Hydrochloric Acid → 4-[(E)-3-oxo-3-(2-phenylamino-6-trifluoromethyl-pyridin-3-yl)-propenyl]-benzoic acid methyl ester

HRID 1261775Notes

Reaction equation

[C:1]1([NH:7][C:8]2[C:13]([C:14](=[O:16])[CH3:15])=[CH:12][CH:11]=[C:10]([C:17]([F:20])([F:19])[F:18])[N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:21]([C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=1)=O.C[O-].[Na+].Cl>CO.O>[CH3:30][O:29][C:27](=[O:28])[C:26]1[CH:31]=[CH:32][C:23](/[CH:21]=[CH:15]/[C:14](=[O:16])[C:13]2[C:8]([NH:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:9][C:10]([C:17]([F:20])([F:18])[F:19])=[CH:11][CH:12]=2)=[CH:24][CH:25]=1

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of 1-(2-phenylamino-6-trifluoromethyl-pyridin-3-yl)-ethanone (4.28 g, 15.3 mmol) in methanol (60.4 mL) at 25° C. was treated with methyl 4-formylbenzoate (3.01 g, 18.3 mmol) and sodium methoxide in methanol (25% wt, 6.99 mL, 30.5 mmol). The reaction was stirred at 25° C. for 2 d. At this time, the reaction was diluted with water (50 mL), neutralized with a 2N aqueous hydrochloric acid solution, and extracted with methylene chloride (3×75 mL). The combined organics were dried over sodium sulfate and filtered. Silica gel was added to the filtrate, concentrated in vacuo and dried under high vacuum. Flash chromatography (40 g silica column, 10-100% ethyl acetate/hexanes) afforded 4-[(E)-3-oxo-3-(2-phenylamino-6-trifluoromethyl-pyridin-3-yl)-propenyl]-benzoic acid methyl ester (4.04 g, 62%) as an orange solid.

Workup

extractionextracted with methylene chloride (3×75 mL)
dry with materialThe combined organics were dried over sodium sulfate
filtrationfiltered
additionSilica gel was added to the filtrate
concentrationconcentrated in vacuo
customdried under high vacuum

Sources & evidence

ORD record: ord-77955051f00b42aa9ab4f7567aa65017
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08471027B2

Reaction notes

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