Methyl Nicotinate → 1,4-Dihydro-1-ethoxycarbonyl-4-(4'-fluorophenyl)-3-methoxycarbonylpyridine

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Reaction Steps

Ethyl chloroformate (3.5 ml) was added to a stirred suspension of cuprous chloride (0.33 g) in dry tetrahydrofuran (100 ml) under nitrogen. After cooling to 0°, a solution of methyl nicotinate (5.0 g) in tetrahydrofuran (10 ml) was added slowly followed by the addition of 4-fluorophenyl magnesium bromide solution [from 4-bromo-fluorobenzene (4.4 ml) and magnesium (0.93 g) in tetrahydrofuran (25 ml)]. After stirring for 20 minutes, the mixture was diluted with ethyl acetate and decomposed by the addition of a saturated ammonium chloride/ammonia solution (1:1, 100 ml). The organic phase was washed with dilute acid and brine and dried over anhydrous sodium sulphate. Evaporation of the solvent gave 1,4-dihydro-1-ethoxycarbonyl-4-(4'-fluorophenyl)-3-methoxycarbonylpyridine as an off-white solid (10.37 g, 93%). A sample crystallised from ethyl acetate had m.p. 83-85°.

Provenance & Evidence