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

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the alcohol of Step 4 (28.2 g, 0.20 mol) and triethylamine (82 mL, 0.59 mol) in dichloromethane (1 L) cooled to -40° C. was added methanesulfonyl chloride (43.5 mL, 0.3 mol). The reaction mixture was warmed to -10° C. for 20 min and then an aqueous solution of NaHCO3 was added. The product was extracted with CH2Cl2, washed with brine and dried over Na2SO4. A portion of this mesylate (0.053 mol) was then dissolved in DMF (180 mL) and cooled to 0° C. Freshly prepared cesium thiol acetate (J. Org. Chem., 51, 3664, (1986)) (22 g, 0.11 mol) was added and the mixture was stirred overnight at r.t. The reaction mixture was poured into an aqueous solution of NaHCO3 and extracted with Et2O. The organic phases were washed with brine and dried over Na2SO4. The residual oil was then purified by flash chromatography with 10:1 hexane:EtOAc to yield 7.5 g, 70%, of the title compound. The product was extracted with CH2Cl2 washed with brine dried over Na2SO4 cooled to 0° C extracted with Et2O The organic phases were washed with brine dried over Na2SO4 The residual oil was then purified by flash chromatography with 10:1 hexane EtOAc to yield 7.5 g, 70%

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The nitrile of Step 3 (0.388 mol) was dissolved in ethanol (400 mL), 8N KOH (800 mL) was added and the reaction mixture was heated to reflux overnight. Most of the ethanol was evaporated and ice was added to the mixture. Concentrated HCl was added (600 mL) dropwise at 0° C. (without warming over 10° C. inside the solution) until obtention of pH ≈1. The acid was then extracted with EtOAc two times and the organic phases were washed 2 times with brine and dried over Na2SO4. The solvent was evaporated and the solid was dissolved in THF (500 mL). A solution of diazomethane in Et2O (about 1.7 L, 0.85 mol) was added at 0° C. until the yellow color remained and no more acid can be seen by TLC. The solvent was evaporated and the residual oil was purified by flash chromatography using 1:1 to 2:1 EtOAc:hexane to yield 28.2 g, (50% yield) of the title compound. the reaction mixture was heated to reflux overnight Most of the ethanol was evaporated ice was added to the mixture Concentrated HCl was added (600 mL) dropwise at 0° C. ( The acid was then extracted with EtOAc two times the organic phases were washed 2 times with brine dried over Na2SO4 The solvent was evaporated the solid was dissolved in THF (500 mL) The solvent was evaporated the residual oil was purified by flash chromatography

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the alcohol of Step 4 (28.2 g, 0.20 mol) and triethylamine (82 mL, 0.59 mol) in dichloromethane (1 L) cooled to -40° C. was added methanesulfonyl chloride (43.5 mL, 0.3 mol). The reaction mixture was warmed to -10° C. for 20 min and then an aqueous solution of NaHCO3 was added. The product was extracted with CH2Cl2, washed with brine and dried over Na2SO4. A portion of this mesylate (0.053 mol) was then dissolved in DMF (180 mL) and cooled to 0° C. Freshly prepared cesium thiol acetate (J. Org. Chem., 51, 3664, (1986)) (22 g, 0.11 mol) was added and the mixture was stirred overnight at r.t. The reaction mixture was poured into an aqueous solution of NaHCO3 and extracted with Et2O. The organic phases were washed with brine and dried over Na2SO4. The residual oil was then purified by flash chromatography with 10:1 hexane:EtOAc to yield 7.5 g, 70%, of the title compound. The product was extracted with CH2Cl2 washed with brine dried over Na2SO4 cooled to 0° C extracted with Et2O The organic phases were washed with brine dried over Na2SO4 The residual oil was then purified by flash chromatography with 10:1 hexane EtOAc to yield 7.5 g, 70%

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The nitrile of Step 3 (0.388 mol) was dissolved in ethanol (400 mL), 8N KOH (800 mL) was added and the reaction mixture was heated to reflux overnight. Most of the ethanol was evaporated and ice was added to the mixture. Concentrated HCl was added (600 mL) dropwise at 0° C. (without warming over 10° C. inside the solution) until obtention of pH≃1. The acid was then extracted with EtOAc two times and the organic phases were washed 2 times with brine and dried over Na2SO4. The solvent was evaporated and the solid was dissolved in THF (500 mL). A solution of diazomethane in Et2O (about 1.7 L, 0.85 mol) was added at 0° C. until the yellow color remained and no more acid can be seen by TLC. The solvent was evaporated and the residual oil was purified by flash chromatography using 1:1 to 2:1 EtOAc:hexane to yield 28.2 g, (50% yield) of the title compound. the reaction mixture was heated to reflux overnight Most of the ethanol was evaporated ice was added to the mixture Concentrated HCl was added (600 mL) dropwise at 0° C. ( The acid was then extracted with EtOAc two times the organic phases were washed 2 times with brine dried over Na2SO4 The solvent was evaporated the solid was dissolved in THF (500 mL) The solvent was evaporated the residual oil was purified by flash chromatography

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the alcohol of Step 10 (28.2 g, 0.20 mol) and triethylamine (82 mL, 0.59 mol) in dichloromethane (1L) cooled to -40° C. was added methanesulfonyl chloride (43.5 mL, 0.3 mol). The reaction mixture was warmed to -10° C. for 20 min and then an aqueous solution of NaHCO3 was added. The product was extracted with CH2Cl2, washed with brine and dried over Na2SO4. A portion of this mesylate (0.053 mol) was then dissolved in DMF (180 mL) and cooled to 0° C. Freshly prepared cesium thiol acetate (J. Org. Chem., 51, 3664, (1986)) (22 g, 0.11 mol) was added and the mixture was stirred overnight at r.t. The reaction mixture was poured into an aqueous solution of NaHCO3 and extracted with Et2O. The organic phases were washed with brine and dried over Na2SO4. The residual oil was then purified by flash chromatography with 10:1 hexane:EtOAc to yield 7.5 g, 70%, of the title compound. The product was extracted with CH2Cl2 washed with brine dried over Na2SO4 cooled to 0° C extracted with Et2O The organic phases were washed with brine dried over Na2SO4 The residual oil was then purified by flash chromatography with 10:1 hexane EtOAc to yield 7.5 g, 70%

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the alcohol of Step 10 (28.2 g, 0.20 mol) and triethylamine (82 mL, 0.59 mol) in dichloromethane (1L) cooled to -40° C. was added methanesulfonyl chloride (43.5 mL, 0.3 mol). The reaction mixture was warmed to -10° C. for 20 min and then an aqueous solution of NaHCO3 was added. The product was extracted with CH2Cl2, washed with brine and dried over Na2SO4. A portion of this mesylate (0.053 mol) was then dissolved in DMF (180 mL) and cooled to 0° C. Freshly prepared cesium thiol acetate (J. Org. Chem., 51, 3664, (1986)) (22 g, 0.11 mol) was added and the mixture was stirred overnight at r.t. The reaction mixture was poured into an aqueous solution of NaHCO3 and extracted with Et2O. The organic phases were washed with brine and dried over Na2SO4. The residual oil was then purified by flash chromatography with 10:1 hexane:EtOAc to yield 7.5 g, 70%, of the title compound. The product was extracted with CH2Cl2 washed with brine dried over Na2SO4 cooled to 0° C extracted with Et2O The organic phases were washed with brine dried over Na2SO4 The residual oil was then purified by flash chromatography with 10:1 hexane EtOAc to yield 7.5 g, 70%

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The nitrile of Step 9 (0.388 mol) was dissolved in ethanol (400 mL), 8N KOH (800 mL) was added and the reaction mixture was heated to reflux overnight. Most of the ethanol was evaporated and ice was added to the mixture. Concentrated HCl was added (600 mL) dropwise at 0° C. (without warming over 10° C. inside the solution) until obtention of pH≃1. The acidic solution was then extracted with EtOAc two times and the organic phases were washed 2 times with brine and dried over Na2SO4. The solvent was evaporated and the solid was dissolved in THF (500 mL). A solution of diazomethane in Et2O (about 1.7L, 0.85 mol) was added at 0° C. until the yellow color remained and no more acid could be seen by TLC. The solvent was evaporated and the residual oil was purified by flash chromatography using 1:1 to 2:1 EtOAc:hexane to yield 28.2 g, (50% yield) of the title compound. the reaction mixture was heated to reflux overnight Most of the ethanol was evaporated ice was added to the mixture Concentrated HCl was added (600 mL) dropwise at 0° C. ( The acidic solution was then extracted with EtOAc two times the organic phases were washed 2 times with brine dried over Na2SO4 The solvent was evaporated the solid was dissolved in THF (500 mL) The solvent was evaporated the residual oil was purified by flash chromatography

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The nitrile of Step 9 (0.388 mol) was dissolved in ethanol (400 mL), 8N KOH (800 mL) was added and the reaction mixture was heated to reflux overnight. Most of the ethanol was evaporated and ice was added to the mixture. Concentrated HCl was added (600 mL) dropwise at 0° C. (without warming over 10° C. inside the solution) until obtention of pH≃1. The acidic solution was then extracted with EtOAc two times and the organic phases were washed 2 times with brine and dried over Na2SO4. The solvent was evaporated and the solid was dissolved in THF (500 mL). A solution of diazomethane in Et2O (about 1.7L, 0.85 mol) was added at 0° C. until the yellow color remained and no more acid could be seen by TLC. The solvent was evaporated and the residual oil was purified by flash chromatography using 1:1 to 2:1 EtOAc:hexane to yield 28.2 g, (50% yield) of the title compound. the reaction mixture was heated to reflux overnight Most of the ethanol was evaporated ice was added to the mixture Concentrated HCl was added (600 mL) dropwise at 0° C. ( The acidic solution was then extracted with EtOAc two times the organic phases were washed 2 times with brine dried over Na2SO4 The solvent was evaporated the solid was dissolved in THF (500 mL) The solvent was evaporated the residual oil was purified by flash chromatography

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of the alcohol of Step 4 (28.2 g, 0.20 mol) and triethylamine (82 mL, 0.59 mol) in dichloromethane (1 L) cooled to -40° C. was added methanesulfonyl chloride (43.5 mL, 0.3 mol). The reaction mixture was warmed to -10° C. for 20 min and then an aqueous solution of NaHCO3 was added. The product was extracted with CH2Cl2, washed with brine and dried over Na2SO4. A portion of this mesylate (0.053 mol) was then dissolved in DMF (180 mL) and cooled to 0° C. Freshly prepared cesium thiol acetate (J. Org. Chem., 2, 3664, (1986)) (22 g, 0.11 mol) was added and the mixture was stirred overnight at r.t. The reaction mixture was poured into an aqueous solution of NaHCO3 and extracted with Et2O. The organic phases were washed with brine and dried over Na2SO4. The residual oil was then purified by flash chromatography with 10:1 hexane:EtOAc to yield 7.5 g, 70%, of the title compound. The product was extracted with CH2Cl2 washed with brine dried over Na2SO4 cooled to 0° C extracted with Et2O The organic phases were washed with brine dried over Na2SO4 The residual oil was then purified by flash chromatography with 10:1 hexane EtOAc to yield 7.5 g, 70%