Cesium carbonate → (S)-2-sec-Butylamino-6-difluoromethoxy-isonicotinic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

Add cesium carbonate (0.352 g, 1.08 mmol) to (S)-2-sec-butylamino-6-hydroxy-isonicotinic acid ethyl ester (0.172 g, 0.72 mmol) in butan-2-one (10 mL) ((Bioorg. Med. Chem. Lett., 12, 2149-2152 (2002)). Heat at 70° C. for 30 min and add chlorodifluoroacetic acid methyl ester (0.24 mL, 2.16 mmol) in three equal portions over 3 h. Heat for 3 days at 70° C. Add again chlorodifluoroacetic acid methyl ester (0.24 mL, 2.16 mmol) in three equal portions over 3 h and stir at room temperature for 24 h. Concentrate and dissolve the crude mixture in ethyl acetate and filter. Purify (silica gel chromatography, eluting with 2:98 to 6:92 ethyl acetate:hexanes) to give the title compound (0.135 g, 65%). MS (ES): m/z=289 [M+H].

Provenance & Evidence