3-(Trifluoromethyl)benzeneacetic acid → N-methoxy-N-methyl-2-[3-(trifluoromethyl)phenyl]acetamide

HRID 2375452Notes

Reaction equation

HRID 2375452 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[C:5]([CH2:9][C:10](O)=[O:11])[CH:6]=[CH:7][CH:8]=1.Cl.[CH3:16][NH:17][O:18][CH3:19].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:19][O:18][N:17]([CH3:16])[C:10](=[O:11])[CH2:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:14])([F:13])[F:1])[CH:4]=1

Participants

6

Reactant 4

HCID 676953-(Trifluoromethyl)benzeneacetic acidHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 22712418N-methoxy-N-methyl-2-[3-(trifluoromethyl)phenyl]acetamideYield 107.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(trifluoromethyl)phenylacetic acid (2.04 g, 10 mmol) and N,O-dimethylhydroxylamine hydrochloride (1.07 g, 11 mmol) in DMF was added HATU (3.8 g, 10 mmol) and DIEA (6.99 ml, 40 mmol) and the resulting yellow solution was stirred at RT for overnight. The crude solution was then extracted with EtOAc and wash with NaHCO3 solution (5%), HCl solution (1:9 v/v) and brine, dried with sodium sulfate and concentrate to afford 2.66 gram of colorless oil as desired compound (4.1) used in the next step without further purification. Rf 0.5 (EtOAc/Hexane 1:1) MS (m/z): 248.1 (M+H), 1H NMR (CDCl3) δ 3.2 (s, 3H), 3.65 (s, 3H), 3.80 (s, 2H), 7.40-7.55 (m, 4H).

Workup

  1. extractionThe crude solution was then extracted with EtOAc
  2. washwash with NaHCO3 solution (5%), HCl solution (1:9 v/v) and brine
  3. dry with materialdried with sodium sulfate
  4. concentrationconcentrate

Sources & evidence

ORD record
ord-0bee0288406741dab69b58b8e8006659
Source dataset
uspto-grants-2008_12
Patent number
US07465755B2

Reaction notes

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