Sodium hydride → 2-(2-Chloro-4-methoxy-phenyl)-3-(2-methyl-pyridin-4-yl)-3-oxo-propionic acid methyl ester

Temperature

50 °C

1,1′-Carbonyldiimidazole (12.35 g) was added to a solution of 2-methylpyridine-4-carboxylic acid (9.95 g, [CAS Reg. No. 4021-11-8]) in DMF (500 mL). The mixture was stirred for 1.5 hours at 50° C. The reaction mixture was cooled to −10° C. in an ice/methanol bath and (2-chloro-4-methoxy-phenyl)-acetic acid methyl ester (15.57 g) (obtained in Example 93, step 1) was added to the light brown solution followed by addition of sodium hydride (50% in mineral oil, 11.59 g) in small portions over 30 minutes. The viscous reaction mixture was stirred at 0° C. for 1.5 hours, until the reaction was complete. The reaction mixture was poured into a sat. NH4Cl solution and extracted two times with ethyl acetate. The organic layers were washed with H2O and brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give the title compound as a yellow oil (13.95 g, 43%). MS (m/e)=334.2 [MH+].

1. temperatureThe reaction mixture was cooled to −10° C. in an ice/methanol bath
2. stirringThe viscous reaction mixture was stirred at 0° C. for 1.5 hours, until the reaction
3. extractionextracted two times with ethyl acetate
4. washThe organic layers were washed with H2O and brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customthe solvent was evaporated
8. customThe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

ORD record

ord-642f910dbc124123ad821a00bcb32cd9

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08138189B2