3-(Trifluoromethyl)aniline → 6-Benzyloxy-benzo[d]isoxazole-3-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 556343Notes

Reaction equation

HRID 556343 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].C[Al](C)C.C([O:18][C:19]([C:21]1[C:25]2[CH:26]=[CH:27][C:28]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:29][C:24]=2[O:23][N:22]=1)=O)C.[NH4+].[Cl-]>C1(C)C=CC=CC=1.C1COCC1.CCOC(C)=O>[F:1][C:2]([F:10])([F:11])[C:3]1[CH:4]=[C:5]([NH:6][C:19]([C:21]2[C:25]3[CH:26]=[CH:27][C:28]([O:30][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[CH:29][C:24]=3[O:23][N:22]=2)=[O:18])[CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 73753-(Trifluoromethyl)anilineHCID 25517Ammonium ChlorideHCID 16682925TrimethylaluminumHCID 669926006-Benzyloxy-benzo[d]isoxazole-3-carboxylic acid ethyl ester

Product 1

HCID 669925996-Benzyloxy-benzo[d]isoxazole-3-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

In a dried vessel, 99 μl (0.79 mMol) 3-trifluoromethyl-aniline are dissolved in 14 ml toluene and cooled to 10° C. Then 1.2 ml Me3Al (2 M in toluene; 2.4 mMol) are added via syringe. After 1 h at rt, a solution of 236 mg (0.79 mMol) 6-benzyloxy-benzo[d]isoxazole-3-carboxylic acid ethyl ester in 3 ml THF is added and the reaction mixture stirred for 25 min in an oil bath at 110° C. The solution is cooled in ice and hydrolyzed with 30 ml of a sat. NH4Cl. After 15 min stirring, EtOAc and Celite are added. The mixture is filtered through Celite, the solid washed with EtOAc and water, the aq. phase separated from the filtrate and extracted with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Crystallisation from EtOAc/hexane gives the title compound: MS: [M−1]=411; TLC(hexane/EtOAc 3:1): Rf=0.51.

Workup

  1. stirringAfter 15 min stirring
  2. filtrationThe mixture is filtered through Celite
  3. washthe solid washed with EtOAc and water
  4. customthe aq. phase separated from the filtrate
  5. extractionextracted with EtOAc
  6. washThe organic layers are washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customCrystallisation from EtOAc/hexane

Sources & evidence

ORD record
ord-0030c59f35d947b78c60274153ee668d
Source dataset
uspto-grants-2011_11
Patent number
US08058276B2

Reaction notes

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