2-Amino-5-fluoro-N-methoxy-N-methylbenzamide → 3-Methylpyridine-2-carboxaldehyde

To a solution of 2-amino-5-fluoro-N-methoxy-N-methylbenzamide (1.0 g, 5.05 mmol) in THF (4.2 mL) was added isopropylmagnesium chloride (2.0M in THF, 5.0 mL, 10.1 mmol) at −40° C. The temperature was allowed to rise to −10° C. over 40 min then was lowered to −40° C. in an acetonitrile/dry ice bath. 3-Methyl-2-pyridinylmagnesium bromide (0.25M in THF, 20.2 mL, 5.0 mmol) was added dropwise and the solution was allowed to rise to rt over one hour. The solution was partitioned between satd ammonium chloride solution and DCM; organic extracts were concentrated then purified by silica gel column chromatography eluting with a gradient of 10-70% EtOAc in hexane to afford 2-amino-5-fluorophenyl)(3-methylpyridin-2-yl)methanone as a yellow oil: LC-MS (ESI) m/z 231.2 [M+H]+.

1. customthen was lowered to −40° C. in an acetonitrile/dry ice bath
2. waitto rise to rt over one hour
3. customThe solution was partitioned between satd ammonium chloride solution and DCM
4. concentrationorganic extracts were concentrated
5. customthen purified by silica gel column chromatography
6. washeluting with a gradient of 10-70% EtOAc in hexane

ORD record

ord-093185e68e544071a1aec297b85ac95c

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765768B2