Dimethylformamide → HCID 21905451, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 1-bromo-3,5-difluorobenzene (16.8 g) in THF (180 ml) was cooled to −75° C. under an argon atmosphere. A 2 M solution of lithiumdiisopropylamide in THF/heptane/ethylbenzene (43.1 ml) was slowly added at below −70° C. The mixture was stirred at −78° C. for 1 h. Dimethylformamide (12.6 ml) was added and the mixture was stirred for 2 h. The cooling bath was removed and the mixture was slowly warmed to rt. The mixture was diluted with diethyl ether and washed with 0.5 M HCl. The aqueous phase was extracted with diethyl ether. The combined organic phase was dried (MgSO4), filtered and the solvent was removed to give the crude 4-bromo-2,6-difluorobenzaldehyde (12.4 g). The crude aldehyde was reacted according to general procedure A using methanol/dioxane as a solvent. The product of this reaction was subsequently coupled with 4-aminomethyl benzonitrile according to general procedure B to give (RS)-2-(4-bromo-2,6-difluoro-phenyl)-N-(4-cyano-benzyl)-2-methoxy-acetamide. Yellow oil. MS 395.0 ([M+H]+)

Provenance & Evidence