Carbon Dioxide → 2-Bromo-5-methoxyisonicotinic acid

HRID 2201535Notes

Reaction equation

N(C(C)C)C(C)C.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][N:10]=1.[Li+].CC([N-]C(C)C)C.[C:25](=[O:27])=[O:26].[OH-].[Na+]>C1COCC1>[Br:8][C:9]1[CH:14]=[C:13]([C:12]([O:15][CH3:16])=[CH:11][N:10]=1)[C:25]([OH:27])=[O:26]

Participants

Conditions

Temperature: 0 °C

Procedure

N-BuLi (21.3 mL, 2.5 M in hexane, 53.2 mmol) was added dropwise to a solution of i-Pr2NH (5.9 g, 58.5 mmol) in THF (80 mL) at −78° C. The solution was stirred at 0° C. for 1 h. A solution of 2-bromo-5-methoxypyridine (10 g, 53.2 mmol) in THF (30 mL) was added dropwise to the LDA solution at −78° C. The mixture was stirred at −78° C. for 2 h and poured onto an excess of dry ice and allowed to warm to RT before being treated with NaOH (5% a.q., 100 mL). The mixture was washed with DCM and acidified to pH 4 by addition of HCl (6 N, 20 mL). The solids were collected by filtration to give the product of 2-bromo-5-methoxyisonicotinic acid (10 g, yield: 83%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.34 (s, 1H), 7.70 (s, 1H), 3.92 (s, 3H). MS (M+H)+: 232/233.

Workup

stirringThe mixture was stirred at −78° C. for 2 h
temperatureto warm to RT
washThe mixture was washed with DCM
additionacidified to pH 4 by addition of HCl (6 N, 20 mL)
filtrationThe solids were collected by filtration

Sources & evidence

ORD record: ord-e2fbf7b2b68e4e2f9a4355182d57e55e
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09364482B2

Reaction notes

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