Sodium Hydroxide → HCID 11809522, compound

1-Benzyloxycarbonyl-4-(R)-(1-ethoxycarbonylcyclopropyl)-3,3-difluoropyrrolidine (2.287 g, 6.472 mmol) was dissolved in ethanol (65 ml) to which, while cooling in an ice bath, was added dropwise a 10 N sodium hydroxide aqueous solution (6.5 ml). The reaction solution was stirred at room temperature for 16 hours and then ethanol was evaporated under reduced pressure. The thus obtained residue was mixed with water (50 ml) and washed with dichloromethane (50 ml×2), and the thus separated aqueous layer was cooled in an ice bath, acidified by adding dropwise concentrated hydrochloric acid and then extracted with diethyl ether (100 ml×5), subsequently drying the extract over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the thus obtained residue was dissolved in benzene (100 ml) and again concentrated under reduced pressure. This azeotropic treatment with benzene was repeated 3 times to obtain 1.956 g (92.9%) of the title compound as a colorless oil.

1. temperaturewhile cooling in an ice bath
2. customethanol was evaporated under reduced pressure
3. additionThe thus obtained residue was mixed with water (50 ml)
4. washwashed with dichloromethane (50 ml×2)
5. temperaturethe thus separated aqueous layer was cooled in an ice bath
6. additionby adding dropwise concentrated hydrochloric acid
7. extractionextracted with diethyl ether (100 ml×5)
8. customsubsequently drying the
9. extractionextract over anhydrous magnesium sulfate
10. filtrationAfter filtration
11. concentrationthe filtrate was concentrated under reduced pressure
12. dissolutionthe thus obtained residue was dissolved in benzene (100 ml)
13. concentrationagain concentrated under reduced pressure

ORD record

ord-a5ad5175cd1842cea1992df2e2b47ad0

Source dataset

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06184388B2