Acetic Acid → Methyl 2-{[(2-bromopyridin-4-yl)methyl]amino}benzoate

HRID 1434707Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:11])[C:4]1[C:5](=[CH:7][CH:8]=[CH:9][CH:10]=1)[NH2:6].C(O)(=O)C.[Br:16][C:17]1[CH:22]=[C:21]([CH:23]=O)[CH:20]=[CH:19][N:18]=1.C([BH3-])#N.[Na+]>CO.O>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH:6][CH2:23][C:21]1[CH:20]=[CH:19][N:18]=[C:17]([Br:16])[CH:22]=1

Participants

Conditions

Temperature: 40 °C

Procedure

6.04 g (40 mmol) of anthranilic acid methyl ester in 600 ml of methanol is mixed with 3.2 ml of acetic acid and 7.4 g (40 mmol) of 2-bromopyridine-4-carbaldehyde and stirred overnight at 40° C. 3.8 g (60 mmol) of sodium cyanoborohydride is added thereto and stirred overnight at 40° C. 3.8 g (60 mmol) of sodium cyanoborohydride is added again and stirred over the weekend at 40° C. It is mixed with water and largely concentrated by evaporation. The aqueous phase is extracted with ethyl acetate, and the combined organic phases are dried, filtered and concentrated by evaporation. The crude product is chromatographed on silica gel with a gradient that consists of hexane and hexane/ethyl acetate 1:3 and hexane/ethyl acetate 1:1 as an eluant. 10.0 g (78% of theory) of 2-[(2-bromo-pyridin-4-ylmethyl)-amino]-benzoic acid methyl ester is obtained as a colorless oil.

Workup

stirringstirred overnight at 40° C
stirringstirred over the weekend at 40° C
concentrationlargely concentrated by evaporation
extractionThe aqueous phase is extracted with ethyl acetate
customthe combined organic phases are dried
filtrationfiltered
concentrationconcentrated by evaporation
customThe crude product is chromatographed on silica gel with a gradient that

Sources & evidence

ORD record: ord-efe6298ef2a6454390c161a4b46437d7
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07615565B2

Reaction notes

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