Methanol → HCID 59894515, compound

Participants

Reaction Conditions

Reaction Steps

A pressure vessel charged with 6-bromo-3-methoxy-2-methyl-pyridine (3.12 g, 15.44 mmol), diacetoxypalladium (346.6 mg, 1.54 mmol), 3-diphenylphosphanylpropyl-diphenyl-phosphane (656.5 mg, 1.54 mmol), triethylamine (6.89 mL, 49.41 mmol) and N,N-dimethyl formamide (42 mL) was treated with methanol (32.53 mL, 802.9 mmol). The vessel was charged to 90 psi with carbon monoxide (432.5 mg, 15.44 mmol) and then vented. This operation was repeated twice. The reaction was charged to 90 psi and heated at 60° C. for 21 hours. The reaction mixture was allowed to cool to 25° C. and was vented. The solvent was evaporated under reduced pressure before ethyl acetate (200 mL) and water (100 mL) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (2×50 mL), dried over sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography utilizing a gradient of 0-50% ethyl acetate in hexane to yield methyl 5-methoxy-6-methylpicolinate (2.47 g, 88%) as a white solid. 1H NMR (400 MHz, DMSO) δ 7.94 (d, J=8.5 Hz, 1H), 7.45 (d, J=8.6 Hz, 1H), 3.90 (s, 3H), 3.83 (s, 3H), 2.40 (s, 3H). ESI-MS m/z calc. 181.1, found 182.3 (M+1)+; Retention time: 0.97 minutes (3 min run).

Provenance & Evidence