tert-Butyl(3R)-3-fluoromethyl-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate → (3R)-3-Fluoromethyl-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid

To a solution of tert-butyl (3R)-3-fluoromethyl-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate (910 mg, 2.71 mmol) in dichloromethane (9 mL), trifluoroacetic acid (9 mL) was added dropwise in an ice bath, and the mixture was stirred at room temperature for 3 hours. After concentrating the reaction mixture under reduced pressure, saturated aqueous solution of sodium hydrogencarbonate (20 mL) was added to the concentrate in an ice bath, and the aqueous solution was washed with diethylether (50 mL). To the aqueous layer was added 1 mol/l hydrochloric acid to pH 2 to 3 in an ice bath, and the solution was extracted with chloroform (100 mL×2). The organic layer was washed with saturated aqueous solution of sodium chloride (100 mL), and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The concentrate was azeotropically distilled by adding toluene (20 mL), and dried under reduced pressure to obtain 910 mg (quantitative) of the title compound as a white solid.

1. concentrationAfter concentrating the reaction mixture under reduced pressure, saturated aqueous solution of sodium hydrogencarbonate (20 mL)
2. additionwas added to the
3. concentrationconcentrate in an ice bath
4. washthe aqueous solution was washed with diethylether (50 mL)
5. additionTo the aqueous layer was added 1 mol/l hydrochloric acid to pH 2 to 3 in an ice bath
6. extractionthe solution was extracted with chloroform (100 mL×2)
7. washThe organic layer was washed with saturated aqueous solution of sodium chloride (100 mL)
8. dry with materialdried with anhydrous sodium sulfate
9. filtrationAfter filtration
10. concentrationthe filtrate was concentrated under reduced pressure
11. distillationThe concentrate was azeotropically distilled
12. additionby adding toluene (20 mL)
13. customdried under reduced pressure

ORD record

ord-3943e9772c5b47a791d8f01d50eb6c7c

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08476429B2