Methanol → Methyl tetrahydro-2-furancarboxylate, (S)-

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Reaction Steps

(2S)-Tetrahydrofuran-2-carboxylic acid (806.2 g) was dissolved in methanol (1779.6 g), and concentrated sulfuric acid (32 mL) was added dropwise at 22° C.-35° C. The reaction solution was heated to 72° C.-75° C., and stirred for 11 hr. The reaction mixture was cooled to room temperature, and partitioned by adding water (5 L) and dichloromethane (5 L). The organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over sodium sulfate. After evaporation of the solvent, the residue was purified by distillation to give methyl (2S)-tetrahydrofuran-2-carboxylate (773.2 g) as a colorless oil. THF (7.4 L) was cooled in an ice-salt-acetone bath, and lithium aluminum hydride (151.0 g) was added by portions. Thereto was added dropwise a solution of methyl (2S)-tetrahydrofuran-2-carboxylate (773.0 g) obtained earlier in THF at an inside temperature of 0° C.-10° C., and the mixture was stirred at an inside temperature of 3° C.-5° C. for 2 hr. Water (150 mL) was added dropwise to the reaction mixture at an inside temperature of 2° C.-4° C., and the reaction was quenched by dropwise addition of 15% aqueous sodium hydroxide solution (150 mL) and water (450 mL), maintained at the same temperature. The insoluble material was filtered off, and washed with THF (2 L), and the filtrate was concentrated under reduced pressure. Thereto were added dichloromethane (3 L) and saturated brine (1.5 L). The organic layer was separated and the aqueous layer was extracted 3 times with dichloromethane. The organic layers were combined, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (567.3 g, yield 90%) as a colorless oil.

Provenance & Evidence