甲基 2-(3-氯-4-甲基硫基苯基)乙酸甲酯

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diisopropylamine (0.23 mL, 1.63 mmol) in dry tetrahydrofuran (5.0 mL) cooled to −78° C. under nitrogen was treated with a 2.5M solution of n-butyllithium in hexanes (0.65 mL, 1.63 mmol). The reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (prepared as in Example 4, 340 mg, 1.48 mmol) in dry tetrahydrofuran (3.0 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.0 mL). The reaction mixture turned dark in color and was allowed to stir at −78° C. for 1 h, at which time, a solution of 8-iodomethyl-1,4-dioxa-spiro[4.5]decane (500 mg, 1.78 mmol) in a small amount of dry tetrahydrofuran was added dropwise. The reaction mixture was allowed to warm to 25° C., where it was stirred for 24 h. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution and then concentrated in vacuo to remove tetrahydrofuran. The aqueous residue was acidified using a 10% aqueous hydrochloric acid solution. The resulting aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S Silica 8/2 hexanes/ethyl acetate) afforded the 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(1,4-dioxa-spiro[4.5]dec-8-yl)-propionic acid methyl ester (315 mg, 55%) as a yellow viscous oil: EI-HRMS m/e calcd for C19H25ClO4S (M+) 384.1162. found 384.1169. to stir at −78° C. for 1 h, at which time to warm to 25° C. where it was stirred for 24 h The reaction mixture was quenched with a saturated aqueous ammonium chloride solution concentrated in vacuo to remove tetrahydrofuran The resulting aqueous layer was extracted with ethyl acetate (2×100 mL) The combined organic extracts were dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diisopropylamine (1.9 mL, 13.64 mmol) in dry tetrahydrofuran (19.5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (6.5 mL) cooled to −78° C. under nitrogen was treated with a 2.5M solution of n-butyllithium in hexanes (5.5 mL, 13.64 mmol). The reaction mixture was stirred at −78° C. for 45 min and then treated dropwise with a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (prepared as in Example 4, 2.42 g, 10.49 mmol) in dry tetrahydrofuran (19.5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (6.5 mL). The reaction mixture turned bright yellow. The reaction mixture was allowed to stir at −78° C. for 15 min, then at 0° C. for an additional 30 min, and then re-cooled to −78° C. At this point, a solution of 2-iodomethyl-6,10-dioxa-spiro[4.5]decane (prepared as in Example 43, 3.85 g, 13.64 mmol) in dry tetrahydrofuran (10 ML) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (3 mL) was added dropwise. The reaction mixture stirred at −78° C. for 30 min and was then allowed to warm to 25° C., where it was stirred for 24 h. The reaction mixture was concentrated in vacuo to remove tetrahydrofuran. The aqueous residue was diluted with ethyl acetate (200 mL), and the organic layer was washed with a saturated aqueous lithium chloride solution (2×200 mL), water (200 mL), and a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 25% ethyl acetate/hexanes) afforded the 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(6,10-dioxa-spiro[4.5]dec-2-yl)-propionic acid methyl ester (2.27 g, 56%) as a yellow oil: EI-HRMS m/e calcd for C19H25ClO4S (M)+ 384.1162. found 384.1181. to stir at −78° C. for 15 min at 0° C. for an additional 30 min re-cooled to −78° C The reaction mixture stirred at −78° C. for 30 min to warm to 25° C. where it was stirred for 24 h The reaction mixture was concentrated in vacuo to remove tetrahydrofuran The aqueous residue was diluted with ethyl acetate (200 mL) the organic layer was washed with a saturated aqueous lithium chloride solution (2×200 mL), water (200 mL) The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diisopropylamine (0.33 mL, 2.38 mmol) in tetrahydrofuran (6 mL) cooled to −78° C. under an argon atmosphere was treated with a 2.5M solution of n-butyllithium in hexanes (0.95 mL, 2.38 mmol). The reaction mixture was stirred at −78° C. for 15 min, after which time, a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (prepared as in Example 4, 500 mg, 2.17 mmol) in tetrahydrofuran (1 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.5 mL) was slowly added via a cannula. The greenish yellow solution was allowed to stir at −78° C. for 1 h, after which time, a solution of 4-iodomethyl-tetrahydro-pyran (588 mg, 2.60 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.5 mL) was added via a cannula. The reaction mixture was then allowed to warm to 25° C., where it was stirred for 16 h. The reaction mixture was then quenched by the addition of a saturated aqueous ammonium chloride solution (30 mL). This solution was extracted with ethyl acetate 3×20 mL). The combined organic layers were washed with a 10% aqueous sulfuric acid solution (2×50 mL) and a saturated aqueous sodium bicarbonate solution (2×50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 75/25 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid methyl ester (431 mg, 61%) as a yellow oil: EI-HRMS m/e calcd for C16H21ClO3S (M+) 328.0900. found 328.0898. to stir at −78° C. for 1 h to warm to 25° C. where it was stirred for 16 h The reaction mixture was then quenched by the addition of a saturated aqueous ammonium chloride solution (30 mL) This solution was extracted with ethyl acetate 3×20 mL) The combined organic layers were washed with a 10% aqueous sulfuric acid solution (2×50 mL) a saturated aqueous sodium bicarbonate solution (2×50 mL), dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diisopropylamine (0.33 mL, 2.38 mmol) in tetrahydrofuran (6 mL) cooled to −78° C. under an argon atmosphere was treated with a 2.5M solution of n-butyllithium in hexanes (0.95 mL, 2.38 mmol). The reaction mixture was stirred at −78° C. for 15 min, after which time, a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (prepared as in Example 4, 500 mg, 2.17 mmol) in tetrahydrofuran (1 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.5 mL) was slowly added via a cannula. The greenish yellow solution was allowed to stir at −78° C. for 1 h, after which time, a solution of 4-iodomethyl-tetrahydro-pyran (588 mg, 2.60 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.5 mL) was added via a cannula. The reaction mixture was then allowed to warm to 25° C., where it was stirred for 16 h. The reaction mixture was then quenched by the addition of a saturated aqueous ammonium chloride solution (30 mL). This solution was extracted with ethyl acetate 3×20 mL). The combined organic layers were washed with a 10% aqueous sulfuric acid solution (2×50 mL) and a saturated aqueous sodium bicarbonate solution (2×50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 75/25 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid methyl ester (431 mg, 61%) as a yellow oil: EI-HRMS m/e calcd for C16H21ClO3S (M+) 328.0900. found 328.0898. to stir at −78° C. for 1 h to warm to 25° C. where it was stirred for 16 h The reaction mixture was then quenched by the addition of a saturated aqueous ammonium chloride solution (30 mL) This solution was extracted with ethyl acetate 3×20 mL) The combined organic layers were washed with a 10% aqueous sulfuric acid solution (2×50 mL) a saturated aqueous sodium bicarbonate solution (2×50 mL), dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diisopropylamine (0.84 mL, 5.98 mmol) in tetrahydrofuran (10 mL) was cooled to −78° C. under an argon atmosphere and then was treated with a 2.5M solution of n-butyllithium in hexanes (2.29 mL, 5.72 mmol). The reaction mixture was stirred at −78° C. for 15 min. At this time, the reaction was slowly treated with a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (prepared as in Example 4, 1.20 g, 5.20 mmol) in tetrahydrofuran (5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.75 mL). The bright yellow solution was allowed to stir at −78° C. for 1 h, after which time, a solution of 3-iodomethyl-tetrahydro-furan (2.21 g, 10.4 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.69 mL) and tetrahydrofuran (5 mL) was added via a cannula. The reaction mixture was then allowed to warm to 25° C., where it was stirred for 48 h. The reaction mixture was then quenched by the addition of a saturated aqueous ammonium chloride solution (30 mL) and extracted with ethyl acetate 3×30 mL). The organic layers were then combined and washed with a 10% aqueous sulfuric acid solution (25 mL) and a saturated aqueous sodium bicarbonate solution (25 mL). The combined organic layers were then dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 75/25 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(tetrahydro-furan-3-yl-propionic acid methyl ester (663 mg, 41%) as a light yellow oil: EI-HRMS m/e calcd for C15H19ClO3S (M+) 314.0743. found 314.0729. to stir at −78° C. for 1 h to warm to 25° C. where it was stirred for 48 h The reaction mixture was then quenched by the addition of a saturated aqueous ammonium chloride solution (30 mL) extracted with ethyl acetate 3×30 mL) washed with a 10% aqueous sulfuric acid solution (25 mL) The combined organic layers were then dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diisopropylamine (0.55 mL, 3.94 mmol) in dry tetrahydrofuran (10 mL) was cooled to −78° C. under argon and was then treated with a 2.5M solution of n-butyllithium in hexanes (1.51 mL, 3.78 mmol). The reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (0.72 g, 3.15 mmol) in dry tetrahydrofuran (3.5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.2 mL). The reaction mixture turned gold in color and was allowed to stir at −78° C. for 1 h. The reaction mixture was then treated with a solution of trifluoromethanesulfonic acid (R)-tetrahydro-furan-2-yl methyl ester (0.959 g, 4.10 mmol) in dry tetrahydrofuran (2 mL). The reaction mixture was allowed to warm to 25° C., where it was stirred for 52 h. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution (25 mL) and then concentrated in vacuo to remove tetrahydrofuran. The aqueous residue was extracted with ethyl acetate 3×50 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 9/1 hexanes/ethyl acetate eluted to 85/15 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(tetrahydro-furan-2(R)-yl)-propionic acid methyl ester (0.519 g, 52%) as a pale yellow oil: [α]23589=−19.02° (c=0.51, chloroform); EI-HRMS m/e calcd for C15H19ClO3S (M+) 314.0743. found 314.0743. to stir at −78° C. for 1 h to warm to 25° C. where it was stirred for 52 h The reaction mixture was quenched with a saturated aqueous ammonium chloride solution (25 mL) concentrated in vacuo to remove tetrahydrofuran The aqueous residue was extracted with ethyl acetate 3×50 mL) The combined organic extracts were dried over sodium sulfate filtered concentrated in vacuo Flash chromatography (Merck Silica gel 60, 230-400 mesh, 9/1 hexanes/ethyl acetate eluted to 85/15 hexanes/ethyl acetate)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diisopropylamine (0.55 mL, 3.94 mmol) in dry tetrahydrofuran (10 mL) was cooled to −78° C. under argon and was then treated with a 2.5M solution of n-butyllithium in hexanes (1.51 mL, 3.78 mmol). The reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (0.72 g, 3.15 mmol) in dry tetrahydrofuran (3.5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.2 mL). The reaction mixture turned gold in color and was allowed to stir at −78° C. for 1 h. The reaction mixture was then treated with a solution of trifluoromethanesulfonic acid (R)-tetrahydro-furan-2-yl methyl ester (0.959 g, 4.10 mmol) in dry tetrahydrofuran (2 mL). The reaction mixture was allowed to warm to 25° C., where it was stirred for 52 h. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution (25 mL) and then concentrated in vacuo to remove tetrahydrofuran. The aqueous residue was extracted with ethyl acetate 3×50 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 9/1 hexanes/ethyl acetate eluted to 85/15 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(tetrahydro-furan-2(R)-yl)-propionic acid methyl ester (0.519 g, 52%) as a pale yellow oil: [α]23589=−19.02° (c=0.51, chloroform); EI-HRMS m/e calcd for C15H19ClO3S (M+) 314.0743. found 314.0743. to stir at −78° C. for 1 h to warm to 25° C. where it was stirred for 52 h The reaction mixture was quenched with a saturated aqueous ammonium chloride solution (25 mL) concentrated in vacuo to remove tetrahydrofuran The aqueous residue was extracted with ethyl acetate 3×50 mL) The combined organic extracts were dried over sodium sulfate filtered concentrated in vacuo Flash chromatography (Merck Silica gel 60, 230-400 mesh, 9/1 hexanes/ethyl acetate eluted to 85/15 hexanes/ethyl acetate)

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid (7.00 g, 32.30 mmol) in methanol (150 mL) was treated slowly with concentrated sulfuric acid (2.8 mL, 52.65 mmol). The resulting reaction mixture was heated under reflux for 1.5 h. The reaction mixture was allowed to cool to 25° C. and then concentrated in vacuo to remove methanol. The residue was diluted with ethyl acetate (500 mL). The organic phase was successively washed with a saturated aqueous sodium bicarbonate solution (1×200 mL) and a saturated aqueous sodium chloride solution (1×200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (7.41 g, 99.4%) as a light yellow oil: EI-HRMS m/e calcd for C10H11ClO2S (M+) 230.0168. found 230.0166. The resulting reaction mixture was heated under reflux for 1.5 h concentrated in vacuo to remove methanol The residue was diluted with ethyl acetate (500 mL) The organic phase was successively washed with a saturated aqueous sodium bicarbonate solution (1×200 mL) a saturated aqueous sodium chloride solution (1×200 mL), dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diisopropylamine (4.86 mL, 34.70 mmol) in dry tetrahydrofuran (212.3 mL) was cooled to −78° C. and then treated with a 2.5M solution of n-butyllithium in hexanes (13.88 mL, 34.70 mmol). The resulting reaction mixture was stirred at −78° C. for 15 min and then slowly treated with a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (7.28 g, 31.55 mmol) in dry tetrahydrofuran (23.6 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (9.43 mL). The resulting bright yellow solution was allowed to stir at −78° C. for 1 h, at which time, a solution of iodomethylcyclopentane (prepared as in Example 1, 7.95 g, 37.86 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (7.08 mL) was slowly added. The reaction mixture was allowed to warm to 25° C. where it was stirred overnight. The reaction mixture was then quenched with a saturated aqueous ammonium chloride solution (20 mL), and the layers were separated. The aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 19/1 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-cyclopentyl-propionic acid methyl ester (5.74 g, 58.1%) as a colorless oil. The resulting reaction mixture to stir at −78° C. for 1 h, at which time to warm to 25° C. where it was stirred overnight The reaction mixture was then quenched with a saturated aqueous ammonium chloride solution (20 mL) the layers were separated The aqueous layer was extracted with ethyl acetate (3×20 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid (prepared as in Example 1, 8.00 g, 36.92 mmol) in methanol (200 mL) was treated slowly with concentrated sulfuric acid (1 mL). The resulting reaction mixture was heated under reflux overnight. The reaction mixture was allowed to cool to 25° C. and then was concentrated in vacuo to remove methanol. The resulting residue was dissolved with ethyl acetate (50 mL). The organic layer was washed with water (1×50 mL). The water layer was further extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (1×25 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to afford (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (7.28 g, 85.5%) as a yellow oil which was used without further purification: EI-HRMS m/e calcd for C10H11ClO2S (M+) 230.0168, found 230.0166. The resulting reaction mixture was heated under reflux overnight was concentrated in vacuo to remove methanol The resulting residue was dissolved with ethyl acetate (50 mL) The organic layer was washed with water (1×50 mL) The water layer was further extracted with ethyl acetate (3×20 mL) The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (1×25 mL) The organic layer was then dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid (prepared as in Example 1, 8.00 g, 36.92 mmol) in methanol (200 mL) was treated slowly with concentrated sulfuric acid (1 mL). The resulting reaction mixture was heated under reflux overnight. The reaction mixture was allowed to cool to 25° C. and then was concentrated in vacuo to remove methanol. The resulting residue was dissolved with ethyl acetate (50 mL). The organic layer was washed with water (1×50 mL). The water layer was further extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (1×25 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to afford (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (7.28 g, 85.5%) as a yellow oil which was used without further purification: EI-HRMS m/e calcd for C10H11ClO2S (M+) 230.0168, found 230.0166. The resulting reaction mixture was heated under reflux overnight was concentrated in vacuo to remove methanol The resulting residue was dissolved with ethyl acetate (50 mL) The organic layer was washed with water (1×50 mL) The water layer was further extracted with ethyl acetate (3×20 mL) The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (1×25 mL) The organic layer was then dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diisopropylamine (4.86 mL, 34.70 mmol) in dry tetrahydrofuran (212.3 mL) was cooled to −78° C. and then treated with a 2.5M solution of n-butyllithium in hexanes (13.88 mL, 34.70 mmol). The resulting reaction mixture was stirred at −78° C for 15 min and then slowly treated with a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (7.28 g, 31.55 mmol) in dry tetrahydrofuran (23.6 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (9.43 mL). The resulting bright yellow solution was allowed to stir at −78° C. for 1 h, at which time, a solution of iodomethylcyclopentane (7.95 g, 37.86 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (7.08 mL) was slowly added. The reaction mixture was allowed to warm to 25° C. where it was stirred overnight. The reaction mixture was then quenched with a saturated aqueous ammonium chloride solution (20 mL), and the layers were separated. The aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 95/5 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-cyclopentyl-propionic acid methyl ester (5.74 g, 58.1%) as a colorless oil. The resulting reaction mixture to stir at −78° C. for 1 h, at which time to warm to 25° C. where it was stirred overnight The reaction mixture was then quenched with a saturated aqueous ammonium chloride solution (20 mL) the layers were separated The aqueous layer was extracted with ethyl acetate (3×20 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo