十六-5-内尔

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

实验步骤: Thereafter the ice bath was replaced with an acetone-dry ice bath and the reaction mixture was cooled to −78° C. A solution of S-phenyl 10-undecenethioate 2 (55.3 mg, 0.20 mmol) in 250 THF was added dropwise via a syringe over 5 min. After stirring the mixture for 2 h at −78° C., a solution of 5-hexynal 1 (19.2 mg, 0.20 mmol) in 250 μL THF was added dropwise over 25 min via a syringe which was cooled externally by a rubber tube filled with dry ice. The reaction mixture was stirred for 30 min and then gradually warmed up to 0° C. within 75 min. Then 1 mL half-saturated NH4Cl solution was added. was cooled externally by a rubber tube The reaction mixture was stirred for 30 min gradually warmed up to 0° C. within 75 min

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

实验步骤: To a stirred solution of (S)-3-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine (64.4 g, 0.23 mol); sodium triacetoxyborohydride (50.9 g, 0.24 mol) and acetic acid (13 mL, 0.23 mol) in dichloromethane (511 mL) at room temperature, was added a solution of hex-5-yn-1-al (26.14 g, 0.27 mol) in dichloromethane (256 mL). The reaction mixture stirred at room temperature overnight (ca. 8 hours) and then the reaction mixture was quenched by addition of concentrated hydrochloric acid (30 mL) and stirring was continued for 1 hour at room temperature. The mixture was then diluted with water (750 mL) and made basic to pH 5 using 10 N sodium hydroxide (18 mL). The layers were separated and the organic layer was washed with 1 N sodium hydroxide (200 mL). The organic layer was dried over magnesium sulfate (10 g); filtered and then concentrated in vacuo to afford 67.6 g of the title intermediate as a yellow gummy solid (83% yield). the reaction mixture was quenched by addition of concentrated hydrochloric acid (30 mL) stirring was continued for 1 hour at room temperature The mixture was then diluted with water (750 mL) The layers were separated the organic layer was washed with 1 N sodium hydroxide (200 mL) The organic layer was dried over magnesium sulfate (10 g) filtered concentrated in vacuo

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

实验步骤: To a stirred solution of (S)-3-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine (64.4 g, 0.23 mol); sodium triacetoxyborohydride (50.9 g, 0.24 mol) and acetic acid (13 mL, 0.23 mol) in dichloromethane (511 mL) at room temperature, was added a solution of hex-5-yn-1-al (26.14 g, 0.27 mol) in dichloromethane (256 mL). The reaction mixture stirred at room temperature overnight (ca. 8 hours) and then the reaction mixture was quenched by addition of concentrated hydrochloric acid (30 mL) and stirring was continued for 1 hour at room temperature. The mixture was then diluted with water (750 mL) and made basic to pH 5 using 10 N sodium hydroxide (18 mL). The layers were separated and the organic layer was washed with 1 N sodium hydroxide (200 mL). The organic layer was dried over magnesium sulfate (10 g); filtered and then concentrated in vacuo to afford 67.6 g of the title intermediate as a yellow gummy solid (83% yield). the reaction mixture was quenched by addition of concentrated hydrochloric acid (30 mL) stirring was continued for 1 hour at room temperature The mixture was then diluted with water (750 mL) The layers were separated the organic layer was washed with 1 N sodium hydroxide (200 mL) The organic layer was dried over magnesium sulfate (10 g) filtered concentrated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: An oven-dried 250 mL three-necked round-bottomed flask under a nitrogen atmosphere was charged with 3-chlorobenzylphosphonate (3.9 g, 15 mmol) and dry THF (60 mL). The solution was cooled to 0° C. in an ice bath for 15 min, then n-BuLi (12 mL of a 1.6 M n-hexane solution, 19 mmol) was added dropwise over 10 min, via syringe. The mixture was stirred at 0° C. for 30 min, then 5-hexynal (1.0 g, 10 mmol) in dry THF (40 mL) was added. The solution was warmed to room temperature and was stirred for 3 h. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 0.5:9.5). The reaction was quenched by adding saturated aqueous ammonium chloride solution (70 mL). The layers were separated and the aqueous phase was extracted with ether (3×50 mL). The combined organic layers were washed with brine (2×50 mL), dried over Na2SO4, gravity filtered and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 0.5:9.5, to provide 1.11 g of the title compound as a colorless oil in 54% yield. The solution was warmed to room temperature was stirred for 3 h The consumption of the starting material The reaction was quenched by adding saturated aqueous ammonium chloride solution (70 mL) The layers were separated the aqueous phase was extracted with ether (3×50 mL) The combined organic layers were washed with brine (2×50 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 0.5:9.5

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: An oven-dried 250 mL three-necked round-bottomed flask under a nitrogen atmosphere was charged with 3-chlorobenzylphosphonate (4.74 g, 18 mmol) and dry THF (60 mL). The solution was cooled to 0° C. in an ice bath for 15 min, then n-BuLi (12 mL of a 1.6 M n-hexane solution, 19 mmol) was added dropwise over 10 min, via syringe. The mixture was stirred at 0° C. for 30 min, then 5-hexynal (1.0 g, 10 mmol) in dry THF (40 mL) was added. The solution was warmed to room temperature and was stirred for 3 h. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 1:9). The reaction was quenched by adding saturated aqueous ammonium chloride solution (70 mL). The layers were separated and the aqueous phase was extracted with ether (3×50 mL). The combined organic layers were washed with brine (2×50 mL), dried over Na2SO4, gravity filtered and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 0.5:9.5, to provide 1.9 g of the title compound as a colorless oil in a 93% yield. The solution was warmed to room temperature was stirred for 3 h The consumption of the starting material The reaction was quenched by adding saturated aqueous ammonium chloride solution (70 mL) The layers were separated the aqueous phase was extracted with ether (3×50 mL) The combined organic layers were washed with brine (2×50 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 0.5:9.5

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: An oven-dried 250 mL three-necked round-bottomed flask under a nitrogen atmosphere was charged with 3-chlorobenzylphosphonate S6 (4.74 g, 18 mmol) and THF (60 mL). The solution was cooled to 0° C. in an ice bath for 15 min, then n-BuLi (12 mL of a 1.6 M n-hexane solution, 19 mmol) was added dropwise over 10 min via syringe. The mixture was stirred at 0° C. for 30 min, then aldehyde 4 (1.0 g, 10 mmol) in THF (40 mL) was added. The reaction was warmed to rt and was stirred for 3 h. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 1:9). The reaction was quenched by adding sat'd aq ammonium chloride solution (70 mL). The layers were separated and the aqueous phase was extracted with ether (3×50 mL). The combined organic layers were washed with brine (2×50 mL), dried over Na2SO4, gravity filtered, and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 0.5:9.5, to provide 1.9 g of the title compound as a colorless oil in a 93% yield. The reaction was warmed to rt was stirred for 3 h The consumption of the starting material The reaction was quenched by adding sat'd aq ammonium chloride solution (70 mL) The layers were separated the aqueous phase was extracted with ether (3×50 mL) The combined organic layers were washed with brine (2×50 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 0.5:9.5

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: An oven-dried 250 mL three-necked round-bottomed flask under a nitrogen atmosphere was charged with 3-chlorobenzylphosphonate S6 (4.74 g, 18 mmol) and THF (60 mL). The solution was cooled to 0° C. in an ice bath for 15 min, then n-BuLi (12 mL of a 1.6 M n-hexane solution, 19 mmol) was added dropwise over 10 min via syringe. The mixture was stirred at 0° C. for 30 min, then aldehyde 4 (1.0 g, 10 mmol) in THF (40 mL) was added. The reaction was warmed to rt and was stirred for 3 h. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 1:9). The reaction was quenched by adding sat'd aq ammonium chloride solution (70 mL). The layers were separated and the aqueous phase was extracted with ether (3×50 mL). The combined organic layers were washed with brine (2×50 mL), dried over Na2SO4, gravity filtered, and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 0.5:9.5, to provide 1.9 g of the title compound as a colorless oil in a 93% yield. The reaction was warmed to rt was stirred for 3 h The consumption of the starting material The reaction was quenched by adding sat'd aq ammonium chloride solution (70 mL) The layers were separated the aqueous phase was extracted with ether (3×50 mL) The combined organic layers were washed with brine (2×50 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 0.5:9.5

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: An oven-dried 250 mL three-necked round-bottomed flask under a nitrogen atmosphere was charged with 3-chlorobenzylphosphonate (3.9 g, 15 mmol) and THF (60 mL). The solution was cooled to 0° C. in an ice bath for 15 min, then n-BuLi (12 mL of a 1.6 M n-hexane solution, 19 mmol) was added dropwise over 10 min via syringe. The mixture was stirred at 0° C. for 30 min, then aldehyde 4 (1.0 g, 10 mmol) in THF (40 mL) was added. The solution was warmed to rt and was stirred for 3 h. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 0.5:9.5). The reaction was quenched by adding sat'd aq ammonium chloride solution (70 mL). The layers were separated and the aqueous phase was extracted with ether (3×50 mL). The combined organic layers were washed with brine (2×50 mL), dried over Na2SO4, gravity filtered, and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 0.5:9.5, to provide 1.11 g of the title compound as a colorless oil in a 54% yield. The solution was warmed to rt was stirred for 3 h The consumption of the starting material The reaction was quenched by adding sat'd aq ammonium chloride solution (70 mL) The layers were separated the aqueous phase was extracted with ether (3×50 mL) The combined organic layers were washed with brine (2×50 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 0.5:9.5

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: An oven-dried 250 mL three-necked round-bottomed flask under a nitrogen atmosphere was charged with 3-chlorobenzylphosphonate (3.9 g, 15 mmol) and THF (60 mL). The solution was cooled to 0° C. in an ice bath for 15 min, then n-BuLi (12 mL of a 1.6 M n-hexane solution, 19 mmol) was added dropwise over 10 min via syringe. The mixture was stirred at 0° C. for 30 min, then aldehyde 4 (1.0 g, 10 mmol) in THF (40 mL) was added. The solution was warmed to rt and was stirred for 3 h. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 0.5:9.5). The reaction was quenched by adding sat'd aq ammonium chloride solution (70 mL). The layers were separated and the aqueous phase was extracted with ether (3×50 mL). The combined organic layers were washed with brine (2×50 mL), dried over Na2SO4, gravity filtered, and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 0.5:9.5, to provide 1.11 g of the title compound as a colorless oil in a 54% yield. The solution was warmed to rt was stirred for 3 h The consumption of the starting material The reaction was quenched by adding sat'd aq ammonium chloride solution (70 mL) The layers were separated the aqueous phase was extracted with ether (3×50 mL) The combined organic layers were washed with brine (2×50 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 0.5:9.5

反应条件: temp:22.01; pressure:0.00; stir:

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

实验步骤: Hex-5-ynal (20 g, 0.2M) and 1,3-propanedithiol (20 mL, 0.2 mmol) were stirred in 300 mL methylene chloride at 0°-5° C. and HCl(g) was bubbled into the solution for 10 minutes when it became cloudy. The mixture was stirred 2 days after which it was poured onto 100 mL of 10% KOH. The organics were washed again with 10% KOH (25 mL), then brine, and dried (MgSO4) before evaporation at reduced pressure. The residue was Kugelrohr distilled at 0.1 mm, oven 110° C. to give 27 g of product (72%). 1H NMR (CDCl3) δ 1.7-1.8 (m, 2H), 1.8-1.95 (m, 3H), 1.99 (t, J=2.6 Hz, 1H), 2.2-2.25 (m, 2H), 2.8-2.95 (m, 4H), 4.06 (t, J=6.9 Hz, 1H). HCl(g) was bubbled into the solution for 10 minutes when it was poured onto 100 mL of 10% KOH The organics were washed again with 10% KOH (25 mL) brine, and dried (MgSO4) before evaporation at reduced pressure distilled at 0.1 mm, oven 110° C.

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: An oven-dried 250 mL three-necked round-bottomed flask under a nitrogen atmosphere was charged with 3-chlorobenzylphosphonate (3.9 g, 15 mmol) and dry THF (60 mL). The solution was cooled to 0° C. in an ice bath for 15 min, then n-BuLi (12 mL of a 1.6 M n-hexane solution, 19 mmol) was added dropwise over 10 min, via syringe. The mixture was stirred at 0° C. for 30 min, then 5-hexynal (1.0 g, 10 mmol) in dry THF (40 mL) was added. The solution was warmed to room temperature and was stirred for 3 h. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 0.5:9.5). The reaction was quenched by adding saturated aqueous ammonium chloride solution (70 mL). The layers were separated and the aqueous phase was extracted with ether (3×50 mL). The combined organic layers were washed with brine (2×50 mL), dried over Na2SO4, gravity filtered and concentrated under reduced pressure. The reaction residue was purified by silica gel flash chromatography, eluting with AcOEt/n-hexane 0.5:9.5, to provide 1.11 g of the title compound as a colorless oil in 54% yield. The solution was warmed to room temperature was stirred for 3 h The consumption of the starting material The reaction was quenched by adding saturated aqueous ammonium chloride solution (70 mL) The layers were separated the aqueous phase was extracted with ether (3×50 mL) The combined organic layers were washed with brine (2×50 mL) dried over Na2SO4, gravity filtered concentrated under reduced pressure The reaction residue was purified by silica gel flash chromatography eluting with AcOEt/n-hexane 0.5:9.5