Dimethylamine → 2-(Dimethylamino)-6-methylpyridine-4-carboxylic acid

Participants

Reaction Steps

Under argon, a solution of 2-chloro-6-methyl-isonicotinic acid tert.-butyl ester (625 mg 2.75 mmol), Na tert.-butylate (396 mg, 4.10 mmol), Xantphos (173 mg, 0.30 mmol) and Pd(OAc)2 (83 mg, 0.37 mmol) in 2 M dimethylamine in THF (35 mL) is stirred at 110° C. for 18 h. The dark reaction mixture is cooled to rt, diluted with 6 N aq. HCl and extracted with diethyl ether (4×60 mL). The org. extracts are concentrated, the residue is dissolved in 6 N aq. HCl and heated to 100° C. for 18 h. The orange suspension is concentrated, dissolved in 1 N aq. NaOH (40 mL) and concentrated again. The residue is dissolved in 1 N aq. NaOH (3 mL) and methanol and separated by MPLC on RP-C18 silica gel to give 2-dimethylamino-6-methyl-isonicotinic acid (1.1 g) as a beige oil; LC-MS: tR=0.44 min, [M+H]+=181.07.

Provenance & Evidence