Ammonia → N-(3-fluorophenyl)-N-(3,3,3-trifluoro-2-hydroxypropyl)-3-(trifluoromethyl)benzamide

HRID 990564Notes

Reaction equation

HRID 990564 reaction equation
FC(F)(F)C1C=C(C=CC=1)C([O:8][CH:9]([CH2:14][N:15]([C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=1)[C:16](=[O:27])[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=1)[C:10]([F:13])([F:12])[F:11])=O.N>CO>[F:34][C:30]1[CH:29]=[C:28]([N:15]([CH2:14][CH:9]([OH:8])[C:10]([F:11])([F:12])[F:13])[C:16](=[O:27])[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)[CH:33]=[CH:32][CH:31]=1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 109519142,2,2-Trifluoro-1-[[(3-fluoro-phenyl)[3-(trifluoromethyl)benzoyl]amino]methyl]ethyl 3-trifluoromethyl-benzoate

Product 1

HCID 10949282N-(3-fluorophenyl)-N-(3,3,3-trifluoro-2-hydroxypropyl)-3-(trifluoromethyl)benzamideYield 61%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2,2,2-trifluoro-1-[[(3-fluorophenyl)[3-(trifluoromethyl)benzoyl]amino]-methyl]ethyl 3-trifluoromethyl-benzoate (600 mg, 1.06 mmol) from EX-662 in methanol was treated with 28% ammonia solution (122 μL). The solution was stirred at room temperature for 10 h. The reaction was quenched with water and extracted with ether. The ether layer was washed with brine and water, then dried over anhydrous MgSO4. The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:8) to give 255 mg (61%) of the desired N-(3-fluorophenyl)-N-(3,3,3-trifluoro-2-hydroxypropyl)-3-(trifluoromethyl)benzamide product as a white powder, 97% pure by HPLC analysis. 1H NMR (CDCl3) δ7.56 (m, 3H), 7.32 (m 2H), 6.98 (m, 1H), 6.90 (m, 2H1), 4.49 (dd, 1H), 4.34 (d, 1H), 4.26 (m, 1H), 4.01 (dd, 1H). 19F NMR (CDCl3) δ−64.7 (s, 3F), −80.3 (s, 3F), −111.0 (m, 1F). HRMS calcd. for C17H12F7NO2: 396.0854 [M+H]+, found: 396.0821.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ether
  3. washThe ether layer was washed with brine and water
  4. dry with materialdried over anhydrous MgSO4
  5. customThe crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:8)

Sources & evidence

ORD record
ord-b25e491db31a4bec99b5c41181066271
Source dataset
uspto-grants-2002_10
Patent number
US06458852B1

Reaction notes

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