N-methyl-2-pyrrolidone → 2-Amino-6-methoxymethyl-nicotinic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-amino-6-chloro-nicotinic acid methyl ester described in Preparation Example A-8 (1.4 g, 7.6 mmol), tributyl-methoxymethyl-stannane (3.1 g, 9.1 mmol) described in Preparation Example A-9, tetrakis(triphenylphosphine)palladium (440 mg, 0.38 mmol) and N-methylpyrrolidinone (20 mL) was stirred at 130° C. for 3.5 hours. The reaction solution was allowed to cool, an aqueous solution of potassium fluoride and ethyl acetate were added thereto on an ice bath, followed by filtering through Celite pad. The organic layer was washed with brine, then, evaporated in vacuo. The residue was purified by silica gel column chromatography (heptane/ethyl acetate=2/1), and the title compound (0.93 g, 4.7 mmol, 63%) was obtained as a light brown oil.

Provenance & Evidence