Trifluoroacetic acid → 4-(2-(2,4-difluorophenoxy)-4-(perfluoroethyl)benzamido)benzoic Acid

HRID 1484187Notes

Reaction equation

F[C:2]1[CH:23]=[C:22]([C:24]([F:30])([F:29])[C:25]([F:28])([F:27])[F:26])[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][C:7]1[CH:19]=[CH:18][C:10]([C:11]([O:13]C(C)(C)C)=[O:12])=[CH:9][CH:8]=1)=[O:5].[F:31][C:32](F)(F)[C:33]([OH:35])=O>ClCCl>[F:31][C:32]1[CH:25]=[C:24]([F:29])[CH:22]=[CH:21][C:33]=1[O:35][C:2]1[CH:23]=[C:22]([C:24]([F:29])([F:30])[C:25]([F:27])([F:28])[F:26])[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][C:7]1[CH:19]=[CH:18][C:10]([C:11]([OH:13])=[O:12])=[CH:9][CH:8]=1)=[O:5]

Participants

Conditions

Temperature: 40 °C

Procedure

The ester obtained in the previous step was dissolved in dichloromethane (1 mL). 2,2,2-Trifluoroacetic acid (4 mL, 52.50 mmol) was added and the reaction was stirred at 40° C. for 18 hours. The excess TFA and dichloromethane was evaporated under reduced pressure. The crude product was filtered and purified by reverse phase preparative chromatography utilizing a gradient of 30-99% acetonitrile in water containing HCl as a modifier to yield 4-(2-(2,4-difluorophenoxy)-4-(perfluoroethyl)benzamido)benzoic acid (2) (31.8 mg, 22%). ESI-MS m/z calc. 487.07. found 488.5 (M+1)+; Retention time: 2.01 minutes (3 minutes run). 1H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 10.92 (s, 1H), 7.98-7.87 (m, 3H), 7.87-7.75 (m, 2H), 7.68-7.59 (m, 1H), 7.57-7.45 (m, 1H), 7.44-7.31 (m, 1H), 7.22-7.13 (m, 1H), 7.11 (s, 1H) ppm.

Workup

customThe excess TFA and dichloromethane was evaporated under reduced pressure
filtrationThe crude product was filtered
custompurified by reverse phase preparative chromatography
additioncontaining HCl as a modifier

Sources & evidence

ORD record: ord-9445fbd4da374985a9d02828dfd6be76
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09421196B2

Reaction notes

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