methyl 2-[1-(sulfanylmethyl)cyclopropyl]acetate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The diol of Step 14 (17.9 g, 46.6 mmol) was dissolved in CH3CN (40 mL) and DMF (10 mL) and cooled to -42° C. under nitrogen. Diisopropyl-ethylamine (8.5 mL, 48.9 mmol) was added followed by methanesulfonyl chloride (3.6 mL, 46.6 mmol) dropwise. The solution was stirred 1.5 hr with a mechanical stirring while maintaining the temperature between -42° and -35° C.; then it was cooled to -45° C. The thiol of Step 9 (7.84 g, 48.9 mmol) was added followed by dropwise addition of DMF (15 mL). Potassium tert-butoxide in THF (56 mL, 1.75M, 97.9 mmol) was added to the reaction mixture over 20 minutes using a syringe pump. Stirring was continued for 5 hr with slow warming from -35° C. to -22° C., giving a very thick translucid gel. The reaction was quenched with saturated aq. NH4Cl (250 mL) and EtOAc (300 mL). The product was extracted with EtOAc, washed with H2O and brine, and dried over MgSO4. Purification by flash chromatography (20% to 30% EtOAc in hexanes) gave 16.8 g (68%) of the title compound. a mechanical stirring while maintaining the temperature between -42° and -35° C. Stirring was continued for 5 hr with slow warming from -35° C. to -22° C. giving a very thick translucid gel The reaction was quenched with saturated aq. NH4Cl (250 mL) and EtOAc (300 mL) The product was extracted with EtOAc washed with H2O and brine dried over MgSO4 Purification by flash chromatography (20% to 30% EtOAc in hexanes)

反応条件: temp:-45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The diol of Step 14 (17.9 g, 46.6 mmol) was dissolved in CH3CN (40 mL) and DMF (10 mL) and cooled to -42° C. under nitrogen. Diisopropyl-ethylamine (8.5 mL, 48.9 mmol) was added followed by methanesulfonyl chloride (3.6 mL, 46.6 mmol) dropwise. The solution was stirred 1.5 hr with a mechanical stirring while maintaining the temperature between -42° and -35° C.; then it was cooled to -45° C. The thiol of Step 9 (7.84 g, 48.9 mmol) was added followed by dropwise addition of DMF (15 mL). Potassium tert-butoxide in THF (56 mL, 1.75M, 97.9 mmol) was added to the reaction mixture over 20 minutes using a syringe pump. Stirring was continued for 5 hr with slow warming from -35° C. to -22° C., giving a very thick translucid gel. The reaction was quenched with saturated aq. NH4Cl (250 mL) and EtOAc (300 mL). The product was extracted with EtOAc, washed with H2O and brine, and dried over MgSO4. Purification by flash chromatography (20% to 30% EtOAc in hexanes) gave 16.8 g (68%) of the title compound. a mechanical stirring while maintaining the temperature between -42° and -35° C. Stirring was continued for 5 hr with slow warming from -35° C. to -22° C. giving a very thick translucid gel The reaction was quenched with saturated aq. NH4Cl (250 mL) and EtOAc (300 mL) The product was extracted with EtOAc washed with H2O and brine dried over MgSO4 Purification by flash chromatography (20% to 30% EtOAc in hexanes)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the nitrile of Step 8 (45 g, 266 mmol) in MeOH (1.36 L) was added H2O(84 mL) and conc. H2SO4 (168 mL). The mixture was heated to reflux for 20 hr, cooled to 25° C., H2O(1 L) was added and the product was extracted with CH2Cl2 (2×1.5 L). The organic extract was washed with H2O and dried over Na2SO4. Concentration of the organic solution gave 36 g (93%) of the title compound. The mixture was heated to reflux for 20 hr the product was extracted with CH2Cl2 (2×1.5 L) The organic extract was washed with H2O dried over Na2SO4

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the nitrile of Step 8 (45 g, 266 mmol) in MeOH (1.36 L) was added H2O(84 mL) and conc. H2SO4 (168 mL). The mixture was heated to reflux for 20 hr, cooled to 25° C., H2O(1 L) was added and the product was extracted with CH2Cl2 (2×1.5 L). The organic extract was washed with H2O and dried over Na2SO4. Concentration of the organic solution gave 36 g (93%) of the title compound. The mixture was heated to reflux for 20 hr the product was extracted with CH2Cl2 (2×1.5 L) The organic extract was washed with H2O dried over Na2SO4

反応条件: temp:20.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 3 L flask, a solution of 1-(mercaptomethyl)cyclopropaneacetic acid (330.7 g) in methanol (1500 ml) was charged. 96% sulfuric acid (36 g) was added, and the reaction mixture was stirred for 5 h at 19-22° C. The reaction mixture was concentrated to ¼ of its volume at 50° C. under reduced pressure, and the residue was partitioned between water (1000 ml) and ethyl acetate (500 ml). The organic phase was separated, washed with 10% NaHCO3 and 5% NaCl (200 ml), and dried overnight over anhydrous sodium sulfate. The mixture was filtered and evaporated at 50° C. under reduced pressure, to afford 315.7 g of the crude 1-(mercaptomethyl)cyclopropaneacetic acid methyl ester, as a colored liquid with a strong, unpleasant odor. The reaction mixture was concentrated to ¼ of its volume at 50° C. under reduced pressure the residue was partitioned between water (1000 ml) and ethyl acetate (500 ml) The organic phase was separated washed with 10% NaHCO3 and 5% NaCl (200 ml) dried overnight over anhydrous sodium sulfate The mixture was filtered evaporated at 50° C. under reduced pressure

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the nitrile of Step 8 (45 g, 266 mmol) in MeOH (1.36 L) was added H2O (84 mL) and cone. H2SO4 (168 mL). The mixture was heated to reflux for 20 hours, cooled to 25° C., H2O (1 L) was added and the product was extracted with CH2Cl2 (2×1.5 L). The organic extract was washed with H2O and dried over Na2SO4. Concentration of the organic solution gave 36 g (93%) of the title compound. The mixture was heated to reflux for 20 hours the product was extracted with CH2Cl2 (2×1.5 L) The organic extract was washed with H2O dried over Na2SO4