Pyridine → Benzamide, 2-fluoro-N-methoxy-N-methyl-3-(trifluoromethyl)-

HRID 735404Notes

Reaction equation

HRID 735404 reaction equation
[F:1][C:2]1[C:10]([C:11]([F:14])([F:13])[F:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].O=S(Cl)Cl.Cl.[CH3:20][NH:21][O:22][CH3:23].N1C=CC=CC=1>C(Cl)Cl>[F:1][C:2]1[C:10]([C:11]([F:14])([F:13])[F:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([N:21]([O:22][CH3:23])[CH3:20])=[O:5]

Participants

6

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 5180022-Fluoro-3-(trifluoromethyl)benzoic acid

Product 1

HCID 11196047Benzamide, 2-fluoro-N-methoxy-N-methyl-3-(trifluoromethyl)-Yield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1.04 g (5 mmol) of 2-fluoro-3-(trifluoromethyl)benzoic acid (compound of formula (III)) 3 ml of SOCl2 were dissolved and the mixture was refluxed for 2 hrs. Remaining SOCl2 was removed in vacuo and the residue (crude acid chloride derivative) was dissolved in 5 ml of CH2Cl2. N,O-Dimethyhydroxylamine hydrochloride (585 mg, 6 mmol) in 8 ml of CH2Cl2 was added followed by 0.5 ml of pyridine. The reaction mixture was stirred for 1.5 hrs., quenched with aq. NH4Cl solution and the product was extracted twice with CH2Cl2, and the combined organic phases were washed with brine and dried over sodium sulfate. Evaporation of solvents in vacuo gave 1.02 g of product as an oil which was pure enough to be used in the next step without further purification.

Workup

  1. temperaturethe mixture was refluxed for 2 hrs
  2. customRemaining SOCl2 was removed in vacuo
  3. dissolutionthe residue (crude acid chloride derivative) was dissolved in 5 ml of CH2Cl2
  4. custom, quenched with aq. NH4Cl solution
  5. extractionthe product was extracted twice with CH2Cl2
  6. washthe combined organic phases were washed with brine
  7. dry with materialdried over sodium sulfate
  8. customEvaporation of solvents in vacuo

Sources & evidence

ORD record
ord-e062fc33b06b44eebd73bc05f8a9c34d
Source dataset
uspto-grants-2009_09
Patent number
US07592363B2

Reaction notes

Loading…