1,1'-Carbonyldiimidazole → HCID 67974926, compound

To a solution of 2-chloro-2-fluorocyclopropanecarboxylic acid (112 g, 809 mmol) in THF (2.0 L) was added 1,1′-carbonyldiimidazole (170 g, 1.05 mmol). The reaction mixture was stirred at room temperature for 1 hour and then (R)-(+)-1-phenylethylamine (117.5 g, 971 mmol) was added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated in vacuo and the residue was extracted with ethyl acetate. The organic extract was washed with 2N aqueous HCl, brine, dried over Na2SO4, filtered and concentrated. The crude product was purified via flash chromatography on silica gel (solvent gradient: 15-33% ethyl acetate in petroleum ether) to yield 2-chloro-2-fluoro-N—((R)-1-phenylethyl)cyclopropanecarboxamide as a white solid (149 g, 50% yield over three steps).

1. stirringThe reaction mixture was stirred at room temperature overnight
2. customThe solvent was evaporated in vacuo
3. extractionthe residue was extracted with ethyl acetate
4. extractionThe organic extract
5. washwas washed with 2N aqueous HCl, brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified via flash chromatography on silica gel (solvent gradient: 15-33% ethyl acetate in petroleum ether)

ORD record

ord-77a237f88bdc480bb4a94a2e52a24532

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08623889B2