Hydrogen Bromide → 4-[(6-Chloropyridin-3-yl)methyl]-1-hydroxy-2-naphthoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 4-[(6-chloropyridin-3-yl)methyl]-1-methoxy-2-naphthoate (see Example 3, 0.200 g, 0.585 mmol) in 5 mL of dichloromethane at −78° C. was added boron tribromide (1.0 M in dichloromethane, 1.76 mL, 1.76 mmol) dropwise. After 1 hour, the reaction was warmed to 0° C., treated with 6 mL of MeOH and warmed to room temperature overnight. To this reaction was added hydrobromic acid (33% in acetic acid, 2.50 mL, 15.2 mmol) dropwise, and the mixture was heated to 65° C. for 60 hours. Addition hydrobromic acid (33% in acetic acid, 1.50 mL, 9.14 mmol) was added, and the reaction was heated to 90° C. for 4 hours, cooled to room temperature, azeotroped 2× with toluene, and concentrated in vacuo to provide 4-[(6-chloropyridin-3-yl)methyl]-1-hydroxy-2-naphthoic acid that gave a mass ion (ES+) of 314.2 for [M+H]+.

Provenance & Evidence