Hydrochloric Acid → tert-butyl(R)-1-benzyloxycarbonyl-4-hydroxy-3-methylpyrrolidine-3-carboxylate

To a solution of tert-butyl (3R)-4-hydroxy-3-methyl-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate (2.00 g, 6.55 mmol) in ethanol (10 mL), 1N hydrochloric acid (6.88 mL, 6.88 mmol) was added at room temperature, and the mixture was stirred for 10 minutes. After concentrating the reaction mixture under reduced pressure and dissolving the residue in ethanol (50 mL), 10% palladium-carbon catalyst (200 mg) was added, and the suspension was stirred in an oil bath at 50° C. for 14 hours in hydrogen atmosphere. After filtering the reaction mixture, the filtrate was concentrated, and the diethylether (30 mL) and saturated sodium hydrogencarbonate (30 mL) were added to the residue, and benzyloxycarbonyl chloride (982 μl, 6.88 mmol) was added in an ice bath. The mixture was stirred at room temperature for 3 hours, and the reaction mixture was extracted with ethyl acetate (100 mL×2). The organic layer was washed with saturated aqueous solution of sodium chloride (20 mL), and dried with anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure and the residue was purified by silica gel column chromatography (hexane : ethyl acetate=2:1→1:2) to obtain 2.00 g (91.1%) of the title compound as a colorless oily substance.

1. concentrationAfter concentrating the reaction mixture under reduced pressure
2. dissolutiondissolving the residue in ethanol (50 mL)
3. addition10% palladium-carbon catalyst (200 mg) was added
4. stirringthe suspension was stirred in an oil bath at 50° C. for 14 hours in hydrogen atmosphere
5. filtrationAfter filtering the reaction mixture
6. concentrationthe filtrate was concentrated
7. additionwas added in an ice bath
8. stirringThe mixture was stirred at room temperature for 3 hours
9. extractionthe reaction mixture was extracted with ethyl acetate (100 mL×2)
10. washThe organic layer was washed with saturated aqueous solution of sodium chloride (20 mL)
11. dry with materialdried with anhydrous sodium sulfate
12. customThe solvent was removed by distillation under reduced pressure
13. customthe residue was purified by silica gel column chromatography (hexane : ethyl acetate=2:1→1:2)

ORD record

ord-4699ef7e445f4cf4b4ff9ded7f4fc541

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08211910B2