Hydrochloric Acid → HCID 69733160, compound

Participants

Reaction Conditions

Reaction Steps

A solution of methyl 5-bromonicotinate (15.0 g, 69.4 mmol) in ethyl acetate is treated with NaH (60% in mineral oil, 2.4 g) and gently heated at 40° C. until a mild exotherm occurs. After cessation of reflux, the reaction mixture is treated with additional NaH (2.27 g, 139 mmol total), heated at reflux temperature for 16 h, cooled to room temperature and diluted with CH2Cl2 and water. The organic phase is separated, washed with brine, dried over Na2SO4 and concentrated in vacuo. The resultant oil is dissolved in acetonitrile and methanol, treated with a 2M solution of trimethylsilyl diazomethane (TMSCHN2) in hexanes (70 ml, 140 mmol), stirred for 36 h and treated with 5% aqueous HCl. After cessation of nitrogen evolution, the phases are separated and the organic phase is washed with brine, dried over Na2SO4 and concentrated in vacuo. The resultant residue is chromatographed through a plug of silica gel (4:1 hexanes:EtOAc) to give the title compound as a light brown solid, 10.1 g (53% yield), identified by HNMR and mass spectral analyses.

Provenance & Evidence