Sodium Hydroxide → 3-Methyl-N-(4-(trifluoromethyl)phenyl)isoxazole-4-carboxamide

HRID 480089Notes

Reaction equation

HRID 480089 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:19])[C:11](=[CH:15][O:16]CC)[C:12]([CH3:14])=O)=[CH:5][CH:4]=1.Cl.[NH2:23]O.[OH-].[Na+]>C(O)C.O>[CH3:14][C:12]1[C:11]([C:10]([NH:9][C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:21])([F:20])[F:1])=[CH:4][CH:5]=2)=[O:19])=[CH:15][O:16][N:23]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 534242632-(Ethoxymethylidene)-3-oxo-N-[4-(trifluoromethyl)phenyl]butanamide

Product 1

HCID 98602203-Methyl-N-(4-(trifluoromethyl)phenyl)isoxazole-4-carboxamideYield 8.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

N-[4-(Trifluoromethyl)phenyl]-2-(ethoxymethylene)-acetoacetamide (4 g) is suspended in 10 mL of ethanol treated with 1.5 g of hydroxylamine hydrochloride in 10 mL of water which has been adjusted to pH 5 with sodium hydroxide. The mixture is stirred and warmed to 40° C. for 2 hours, then cooled to room temperature and the precipitate collected by vacuum filtration. Sodium hydroxide (1 g) is added to the filtrate which is stirred for 30 minutes. The mixture is acidified to pH 2 with 6 N hydrochloric acid and the precipitate collected by vacuum filtration. The filtrate is then diluted with 100 mL of water and allowed to stand at 4° C. overnight. The precipitate is collected by vacuum filtration, washed with ethanol:water 2:1 and dried to give 300 mg of crude 3-methyl-4-[4-(trifluoromethyl)-phenylaminocarbonyl]isoxazole. The crude is purified on a column of silica gel eluting with ethyl acetate:hexane 1:4 to give 100 mg of 3-methyl-4-[4-(trifluoromethyl)phenylaminocarbonyl]-isoxazole, an off-white solid.

Workup

  1. temperaturecooled to room temperature
  2. filtrationthe precipitate collected by vacuum filtration
  3. additionSodium hydroxide (1 g) is added to the filtrate which
  4. stirringis stirred for 30 minutes
  5. filtrationthe precipitate collected by vacuum filtration
  6. additionThe filtrate is then diluted with 100 mL of water
  7. filtrationThe precipitate is collected by vacuum filtration
  8. washwashed with ethanol:water 2:1
  9. customdried

Sources & evidence

ORD record
ord-ea4cf09f4b1c49b6bea493b6b3c6f88b
Source dataset
uspto-grants-2003_11
Patent number
US06649635B2

Reaction notes

Loading…