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

HRID 556346Notes

Reaction equation

HRID 556346 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][Si:31]([CH:38]([CH3:40])[CH3:39])([CH:35]([CH3:37])[CH3:36])[CH:32]([CH3:34])[CH3:33])=[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][Si:31]([CH:35]([CH3:37])[CH3:36])([CH:38]([CH3:40])[CH3:39])[CH:32]([CH3:33])[CH3:34])=[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 669926156-Triisopropylsilanyloxy-benzo[d]isoxazole-3-carboxylic acid ethyl ester

Product 1

HCID 669929826-Triisopropylsilanyloxy-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, 207 μl (1.66 mMol) 3-trifluoromethyl-aniline are dissolved in 28 ml toluene and cooled to 10° C. Then 2.5 ml Me3Al (2 M in toluene; 5.0 mMol) are added via syringe. After 1 h at rt, a solution of 602 mg (1.66 mMol) 6-triisopropylsilanyloxy-benzo[d]isoxazole-3-carboxylic acid ethyl ester in 6 ml THF is added and the reaction mixture stirred for 30 min in an oil bath at 110° C. The solution is cooled in ice and hydrolyzed with 70 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, yielding the title compound as an oil: MS: [M−1]=477; TLC(hexane/EtOAc 19:1): Rf=0.30.

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

Sources & evidence

ORD record
ord-856c57a394474b2aa1456680aa93a00e
Source dataset
uspto-grants-2011_11
Patent number
US08058276B2

Reaction notes

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