Methanol → 4-(2-(4-(trifluoromethoxy)phenoxy)-4-(trifluoromethyl)benzamido)benzoic Acid

HRID 515096Notes

Reaction equation

F[C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:3]=1[C:4]([NH:6][C:7]1[CH:16]=[CH:15][C:10]([C:11]([O:13]C)=[O:12])=[CH:9][CH:8]=1)=[O:5].[OH-:25].[Li+].[CH3:27][OH:28]>>[F:22][C:21]([F:24])([F:23])[O:25][C:2]1[CH:20]=[CH:19][C:27]([O:28][C:2]2[CH:20]=[C:19]([C:21]([F:22])([F:24])[F:23])[CH:18]=[CH:17][C:3]=2[C:4]([NH:6][C:7]2[CH:16]=[CH:15][C:10]([C:11]([OH:13])=[O:12])=[CH:9][CH:8]=2)=[O:5])=[CH:4][CH:3]=1

Participants

Reactant 3

HCID 887Methanol

HCID 3939Lithium Hydroxide

HCID 90314677Methyl 4-[[2-fluoro-4-(trifluoromethyl)benzoyl]amino]benzoate

Product 1

HCID 778440134-(2-(4-(trifluoromethoxy)phenoxy)-4-(trifluoromethyl)benzamido)benzoic AcidYield 37%

Conditions

Temperature: 50 °C

Procedure

To the ester from the previous step were added lithium hydroxide (2M, 450 μL, 0.9 mmol) and methanol (300 μL) and the reaction was stirred at 50° C. for 3 hours. The reaction was filtered and purified by reverse phase preparative chromatography utilizing a gradient of 3 0-99% acetonitrile in water containing HCl as a modifier to yield 4-(2-(4-(trifluoromethoxy)phenoxy)-4-(trifluoromethyl)benzamido)benzoic acid (7) (53.8 mg, 37%). ESI-MS m/z calc. 485.07, found 486.3 (M+1)+; Retention time: 2.05 minutes (3 minutes run). 1H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 10.85 (s, 1H), 7.96-7.86 (m, 3H), 7.78-7.67 (m, 3H), 7.45-7.35 (m, 3H), 7.24-7.17 (m, 2H) ppm.

Workup

filtrationThe reaction was filtered
custompurified by reverse phase preparative chromatography
additioncontaining HCl as a modifier

Sources & evidence

ORD record: ord-c659d3a6ef17449998fd98b1e7d9eda1
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108903B2

Reaction notes

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