Sodium Bicarbonate → N-[2-(S)-(3,4-dichlorophenyl)-4-hydroxybutyl]-N-methyl-3cyano-2methoxy-1-naphthamide

Participants

Reaction Conditions

Reaction Steps

A solution of N-[2-(S)-(3,4-dichlorophenyl)-4-hydroxybutyl]-N-methylamine (Miller, SC; WO 9512577) in DCM was combined with 10% aqueous sodium bicarbonate solution. The mixture was cooled to 0° C. and a solution of 3-cyano-2-methoxy-1-naphthoyl chloride (prepared from 3-cyano-2-methoxy-1-naphthoic acid using oxalyl chloride) in DCM was added dropwise over 30 min. After stirring overnight at room temperature, the organic phase was concentrated and purified by column chromatography to afford N-[2-(S)-(3,4-dichloro-phenyl)-4-hydroxybutyl]-N-methyl-3-cyano-2-methoxy-1-naphathamide. 1H NMR (300 MHz, DMSO-d6) δ 8.67-8.58 (m), 8.07-8.00 (m), 7.72-7.65 (m), 7.64-7.43 (m), 7.42-7.34 (m), 7.02-7.01 (m), 6.98-6.87 (d), 6.77-6.74 (d), 6.31-6.28 (d), 4.55-4.52 (t), 4.35-4.34 (t), 4.03-3.92 (m), 3.78-3.72 (m), 3.68 (s), 3.45-3.37 (m), 3.29-2.89 (m), 2.73 (s), 2.59-2.49 (m), 1.91-1.78 (m), 1.58-1.46 (m); MS APCI, m/z=457 (M+). (g) N-[2-(S)-(3,4-Dichlorophenyl)-3-carboxypropyl]—N-methyl-3-cyano-2-methoxy-1-naphthamide

Provenance & Evidence