Bromocyclopropane → (6-Chloropyridin-3-yl)(cyclopropyl)methanone

To a solution of cyclopropylbromide (1.24 g, 10.24 mmol) in THF (10 mL) was added dropwise a 2.5M solution of n-butyllithium in hexanes (4.0 mL, 10.00 mmol) at −78° C. and the reaction mixture was stirred for 1 h at this temperature. Then a solution of 6-chloro-N-methyl-N-(methyloxy)pyridine-3-carboxamide (1.00 g, 4.98 mmol) in THF (5 mL) was added quickly at −78° C., and the cooling bath was removed. Stirring was continued for 1 h, then the solution was poured into saturated ammonium chloride (100 mL), extracted with ethyl acetate (3×50 mL) and the organic layers were washed with brine (50 mL), dried over sodium sulfate then filtered and concentrated. Column chromatography on silica (hexanes:ethyl acetate 9:1 to 8:2) afforded (6-chloropyridin-3-yl)(cyclopropyl)-methanone (0.62 g, 68% yield). 1H NMR (400 MHz, CDCl3): 9.04 (d, 1H), 8.22 (dd, 1H), 7.46 (d, 1H), 2.61 (m, 1H), 1.32 (m, 2H), 1.15 (m, 2H).

1. customthe cooling bath was removed
2. stirringStirring
3. waitwas continued for 1 h
4. additionthe solution was poured into saturated ammonium chloride (100 mL)
5. extractionextracted with ethyl acetate (3×50 mL)
6. washthe organic layers were washed with brine (50 mL)
7. dry with materialdried over sodium sulfate
8. filtrationthen filtered
9. concentrationconcentrated

ORD record

ord-ee38e2b6633c42e6871581c4abc57cd0

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08012956B2