Acetic Acid → HCID 178454095, compound

Participants

Reaction Steps

The bis-toluenesulfonic acid salt of 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole (48 mg, 0.169 mmol) was dissolved in dry DMA (1.2 mL), tert-butyl[(2R,3S)-2-(2,5-difluorophenyl)-5-oxotetrahydro-2H-thiopyran-3-yl]carbamate (Intermediate 2) (17.3 mg, 0.05 mmol) and triethylamine (65 μL, 0.469 mmol) were added and the solution was stirred at RT for 10 min. Acetic acid (43 μL, 0.75 mmol) was added and the solution was stirred at room temperature for 5 min and then transferred to a 50 degree oil bath. After 5 min, 1M sodium cyanoborohydride in THF (190 μL, 0.19 mmol) was added. After 30 min, the solution was cooled to room temperature and added to a mixture of ethyl acetate (30 mL) and saturated aqueous NaHCO3 (10 mL). The organic phase was washed with water (2×10 mL), brine (1×5 mL), dried with MgSO4., filtered and evaporated to an oil. Examination of the crude oil by HNMR showed an approximately 4:1 ratio of diastereomeric amines at C-5. The oil was purified by 1×500 micron preparative thin layer chromatography using 15:1 methylene chloride/10% ammonium hydroxide in EtOH as developing solvent. The more polar band was removed, eluted with the developing solvent mixture and evaporated to give the title compound.

Provenance & Evidence