Sodium Hydroxide → 1-[1-Benzyloxycarbonyl-4-(R)-fluoro-3-(S)-pyrrolidinyl]cyclopropanecarboxylic acid

1-Benzyloxycarbonyl-4-(R)-(1-ethoxycarbonylcyclopropyl)-3-(S)-fluoropyrrolidine (3.715 g, 11.08 mmol) was dissolved in ethanol (110 ml), and 10 N sodium hydroxide aqueous solution (11 ml) was added dropwise to the thus prepared solution which was cooled in an ice bath. The reaction solution was stirred at room temperature for 18 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). The thus separated aqueous layer was cooled in an ice bath, acidified by adding dropwise concentrated hydrochloric acid, extracted with diethyl ether (100 ml×5) and then dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was dissolved in benzene (100 ml) and again concentrated under reduced pressure. This azeotropic step with benzene was repeated 3 times to obtain 3.346 g (98.3%) of the title compound as a colorless amorphous substance.

1. temperaturewas cooled 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. dry with materialdried over anhydrous magnesium sulfate
9. filtrationAfter filtration
10. concentrationthe filtrate was concentrated under reduced pressure
11. dissolutionthe residue was dissolved in benzene (100 ml)
12. concentrationagain concentrated under reduced pressure

ORD record

ord-5599449102234c64ae48faa98c24f617

Source dataset

uspto-grants-2000_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06121285