2-甲基四氢呋喃-3-酮

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: A three-necked reactor (1 l) that was equipped with a dropping funnel and a condenser and had been dried was charged with 13.1 g (200 mmol) of a zinc powder (special grade, manufactured by Wako Pure Chemical Industries, Ltd.). After replacing the atmosphere inside the reactor with argon, 240 ml of tetrahydrofuran (THF) was added to the reactor. After the addition of 1.9 ml (15 mmol) of chlorotrimethylsilane while stirring the mixture using a magnetic stirrer, the mixture was stirred at 20 to 25° C. for 30 minutes. A solution prepared by dissolving 20.0 g (200 mmol) of 2-methyltetrahydrofuran-3-one in 40 ml of THF was then added to the mixture. Next, a solution prepared by dissolving 34.8 g (180 mmol) of ethyl (2-bromomethyl)acrylate in 50 ml of THF was added dropwise to the mixture. After the addition, the mixture was stirred at room temperature for 2 hours. After confirming completion of the reaction by gas chromatography, an ammonium chloride aqueous solution and ethyl acetate were added to the mixture to effect separation. The resulting organic layer was sequentially washed with water and a saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The concentrate was distilled under reduced pressure to obtain 20.4 g of 6-methyl-3-methylene-1,7-dioxaspiro[4.4]nonan-2-one (compound represented by the formula (Ss-1)) as a transparent oily product. A three-necked reactor (1 l) that was equipped with a dropping funnel and a condenser had been dried was added to the reactor the mixture was stirred at 20 to 25° C. for 30 minutes A solution prepared was then added to the mixture Next, a solution prepared was added dropwise to the mixture After the addition the mixture was stirred at room temperature for 2 hours completion of the reaction by gas chromatography separation The resulting organic layer was sequentially washed with water a saturated sodium chloride solution, dried over magnesium sulfate concentrated under reduced pressure The concentrate was distilled under reduced pressure

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

实验步骤: A three-necked reactor (1 l) that was equipped with a dropping funnel and a condenser and had been dried was charged with 13.1 g (200 mmol) of a zinc powder (special grade, manufactured by Wako Pure Chemical Industries, Ltd.). After replacing the atmosphere inside the reactor with argon, 240 ml of tetrahydrofuran (THF) was added to the reactor. After the addition of 1.9 ml (15 mmol) of chlorotrimethylsilane while stirring the mixture using a magnetic stirrer, the mixture was stirred at 20 to 25° C. for 30 minutes. A solution prepared by dissolving 20.0 g (200 mmol) of 2-methyltetrahydrofuran-3-one in 40 ml of THF was then added to the mixture. Next, a solution prepared by dissolving 34.8 g (180 mmol) of ethyl (2-bromomethyl)acrylate in 50 ml of THF was added dropwise to the mixture. After the addition, the mixture was stirred at room temperature for 2 hours. After confirming completion of the reaction by gas chromatography, an ammonium chloride aqueous solution and ethyl acetate were added to the mixture to effect separation. The resulting organic layer was sequentially washed with water and a saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The concentrate was distilled under reduced pressure to obtain 20.4 g of 6-methyl-3-methylene-1,7-dioxaspiro[4.4]nonan-2-one (compound represented by the formula (Ss-1)) as a transparent oily product. A three-necked reactor (1 l) that was equipped with a dropping funnel and a condenser had been dried was added to the reactor the mixture was stirred at 20 to 25° C. for 30 minutes A solution prepared was then added to the mixture Next, a solution prepared was added dropwise to the mixture After the addition the mixture was stirred at room temperature for 2 hours completion of the reaction by gas chromatography separation The resulting organic layer was sequentially washed with water a saturated sodium chloride solution, dried over magnesium sulfate concentrated under reduced pressure The concentrate was distilled under reduced pressure

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

实验步骤: Prepared in analogy to Example A62(b) from 2-benzyl-5-bromo-2,3-dihydro-1H-isoindole (Example A62(a)) and 2-methyltetrahydrofuran-3-one. Brown oil. MS (m/e): 310.4 ([M+H]+, 100%).

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

实验步骤: Prepared in analogy to Example A62(b) from 2-benzyl-5-bromo-2,3-dihydro-1H-isoindole (Example A62(a)) and 2-methyltetrahydrofuran-3-one. Brown oil. MS (m/e): 310.4 ([M+H]+, 100%).

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: Prepared in analogy to Example A62(b) from 2-benzyl-5-bromo-2,3-dihydro-1H-isoindole (Example A62(a)) and 2-methyltetrahydrofuran-3-one. Brown oil. MS (m/e): 310.4 ([M+H]+, 100%).

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

实验步骤: 3-(2,2,2-Trifluoroacetylamino)thiophene-2-carboxylic acid methyl ester and 2-methyldihydrofuran-3-one were reacted by method M. The product with the molecular weight of 353.32 (C13H14F3NO5S) was obtained in this way; MS (ESI): 354 (M+H+). The product with the molecular weight of 353.32 (C13H14F3NO5S) was obtained in this way

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

实验步骤: To a solution of 5-bromo-3-methyl-1′,2′,3′,6′-tetrahydro-2,4′-bipyridine (2.26 g) described in Reference Example 109 (2) and 2-methyltetrahydrofuran-3-one (1.1 ml) in dichloromethane (25 ml) was added sodium triacetoxyborohydride (2.77 g), and stirred at room temperature for 6 hours. To the reaction solution was added 1 N aqueous solution of sodium hydroxide, and extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated in vacuo. The obtained residue was purified with silica gel chromatography (n-hexane/ethyl acetate) to give cis-4-(5-bromo-3-methyl-pyridin-2-yl)-1-(2-methyltetrahydrofuran-3-yl)-1,2,3,6-tetrahydropyridine (2.43 g) and trans-4-(5-bromo-3-methylpyridin-2-yl)-1-(2-methyltetrahydrofuran-3-yl)-1,2,3,6-tetrahydropyridine (193 mg) as brown oils respectively. MS (ESI) m/z: 337, 339 (M+H)+. extracted with chloroform The obtained organic layer was dried over anhydrous sodium sulfate the solvent was evaporated in vacuo The obtained residue was purified with silica gel chromatography (n-hexane/ethyl acetate)

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

实验步骤: To a solution of 4-(5-bromopyridin-2-yl)piperidine-4-carbonitrile (1.15 g) in toluene (14.4 ml), was added 2-methyltetrahydrofuran-3-one (526 mg), and then, sodium triacetoxyborohydride (1.37 g), and the mixture was stirred at room temperature for five hours. Water and 1N aqueous solution of sodium hydroxide were added to the reaction solution at 0° C., and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified with NH silica gel chromatography (n-hexane/ethyl acetate) to give cis-4-(5-bromopyridin-2-yl)-1-(2-methyltetrahydrofuran-3-yl)piperidine-4-carbonitrile (1.05 g) as a yellow solid. extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous sodium sulfate concentrated in vacuo The residue was purified with NH silica gel chromatography (n-hexane/ethyl acetate)

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

实验步骤: Prepared as described for 7-iodo-3,4,5′,6′-tetrahydro-2H,4′H-spiro[1-benzofuro[2,3-c]pyridine-1,3′-pyran] using 2-(6-iodo-benzofuran-3-yl)-ethylamine and 2-methyldihydrofuran-3(2H)-one. The resulting diasteroisomeric mixture was separated using medium pressure liquid chromatography (140 g amine column) eluting with a gradient of EtOAc in hexanes (from 15% to 70% EtOAc). Prepared The resulting diasteroisomeric mixture was separated eluting with a gradient of EtOAc in hexanes (from 15% to 70% EtOAc)

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

实验步骤: To 15.4 g of 2-aminoethanethiol-HCl (0.13 mole) dissolved into 50 ml of water were added slowly 20 g of 2-methyl-3-tetrahydrofuranone (0.2 mole) (solution pH=2.7). The pH was kept to neutrality by adding 10% aqueous NaOH. After 1 hour, extraction of the water solution with Et2O, drying of the organic phase with MgSO4 and distillation of the crude product (Bp 1.7 mbar, 93°-96° C.) gave 18 g of the desired product (yield=90%). The product was obtained as a mixture of two diastereoisomers (isomers a and b). extraction of the water solution with Et2O drying of the organic phase with MgSO4 and distillation of the crude product (Bp 1.7 mbar, 93°-96° C.)