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

HRID 335062Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([O:19]C)=[C:11]([C:21]([O:23]C)=[O:22])[CH:10]=2)=[CH:4][CH:3]=1.B(Br)(Br)Br.CO.Br>ClCCl>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([OH:19])=[C:11]([C:21]([OH:23])=[O:22])[CH:10]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

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]+.

Workup

temperaturewarmed to room temperature overnight
temperaturethe mixture was heated to 65° C. for 60 hours
additionwas added
temperaturethe reaction was heated to 90° C. for 4 hours
temperaturecooled to room temperature
customazeotroped 2× with toluene
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-004719288acc4816bdde13cae7fc44fe
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883850B2

Reaction notes

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