Pyridine → N-Methoxy-N-methyl-4-(trifluoromethyl)benzamide

HRID 735889Notes

Reaction equation

HRID 735889 reaction equation
Cl.[CH3:2][NH:3][O:4][CH3:5].[F:6][C:7]([F:18])([F:17])[C:8]1[CH:16]=[CH:15][C:11]([C:12](Cl)=[O:13])=[CH:10][CH:9]=1.FC(F)(F)C1C=CC(C(O)=O)=CC=1.N1C=CC=CC=1>O=S(Cl)Cl.C(Cl)Cl>[CH3:5][O:4][N:3]([CH3:2])[C:12](=[O:13])[C:11]1[CH:15]=[CH:16][C:8]([C:7]([F:18])([F:17])[F:6])=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 99664-(Trifluoromethyl)benzoic acidHCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

Product 1

HCID 14069348N-Methoxy-N-methyl-4-(trifluoromethyl)benzamideYield 90%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

To a cold (0° C.) solution of N,O-dimethylhydroxylamine hydrochloride (2.5 g, 25.6 mmol) and 4-(trifluoromethyl)benzoyl chloride (prepared by refluxing a solution of 4-(trifluoromethyl)benzoic acid in SOCl2, 4.86 g, 23.3 mmol) in DCM (50 mL) was added dropwise pyridine (4.06 g, 51.26 mmol). The reaction mixture was stirred overnight and evaporated. The residue was dissolved in a mixture of DCM/Et2O (1/1) (45 mL) and brine (45 mL) was added. The aqueous layer was separated and extracted twice with DCM/Et2O (1/1) (45 mL). The combined organic layers were washed with brine (45 mL), dried over MgSO4, filtered and concentrated under vacuum to give the title compound as a yellow oil (4.88 g, 90%). 1H NMR (CDCl3, 300 MHz) δ 7.90-7.70 (m, 2H), 7.76-7.60 (m, 2H), 3.65-3.45 (m, 3H), 3.43-3.33 (m, 3H). HPLC (Condition A), Rt: 3.41 min (HPLC purity: 98.0%).

Workup

  1. customevaporated
  2. dissolutionThe residue was dissolved in a mixture of DCM/Et2O (1/1) (45 mL) and brine (45 mL)
  3. additionwas added
  4. customThe aqueous layer was separated
  5. extractionextracted twice with DCM/Et2O (1/1) (45 mL)
  6. washThe combined organic layers were washed with brine (45 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-214463a7d41a4a018c1a8626c07c39c0
Source dataset
uspto-grants-2009_09
Patent number
US07592477B2

Reaction notes

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