3-(Trifluoromethyl)aniline → HCID 24763124, compound

HRID 556365Notes

Reaction equation

HRID 556365 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:22]2[CH:29]=[CH:28][C:27]([O:30][C:31]3[CH:36]=[CH:35][N:34]=[C:33]([NH2:37])[N:32]=3)=[CH:26][C:23]=2[S:24][CH:25]=1)=O)C.[NH4+].[Cl-]>C1COCC1>[F:1][C:2]([F:10])([F:11])[C:3]1[CH:4]=[C:5]([NH:6][C:19]([C:21]2[C:22]3[CH:29]=[CH:28][C:27]([O:30][C:31]4[CH:36]=[CH:35][N:34]=[C:33]([NH2:37])[N:32]=4)=[CH:26][C:23]=3[S:24][CH:25]=2)=[O:18])[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 73753-(Trifluoromethyl)anilineHCID 25517Ammonium ChlorideHCID 16682925TrimethylaluminumHCID 57556446HCID 57556446, compound

Product 1

HCID 24763124HCID 24763124, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

In a dried vessel, 66 mg (0.41 mMol) 3-trifluoromethyl-aniline are dissolved in 7 ml degassed toluene and cooled to 10° C. Then 650 μl Me3Al (2 M in toluene; 1.3 mMol) are added via syringe. After 45 min at rt, a solution of 100 mg (0.317 mMol) 6-(2-amino-pyrimidin-4-yloxy)-benzo[b]thiophene-3-carboxylic acid ethyl ester (Step 12.5) in 2.5 ml THF is added and the reaction mixture is stirred for 40 min in an oil bath of 110° C. The solution is cooled in an ice-bath and hydrolyzed with 15 ml of a sat. NH4Cl. After 10 min stirring, the mixture is filtered through Celite, the solid washed extensively 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. Column chromatography (SiO2; EtOAc/hexane 9:1) and crystallization from CH2Cl2/hexane gives the title compound: MS: [M+1]+=431; TLC(EtOAc/hexane 9:1): Rf=0.24.

Workup

  1. customdegassed toluene
  2. stirringAfter 10 min stirring
  3. filtrationthe mixture is filtered through Celite
  4. washthe solid washed extensively with EtOAc and water
  5. customthe aq. phase separated from the filtrate
  6. extractionextracted with EtOAc
  7. washThe organic layers are washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customColumn chromatography (SiO2; EtOAc/hexane 9:1) and crystallization from CH2Cl2/hexane

Sources & evidence

ORD record
ord-7bd71f56a03f499d9eb3147ce2747fc8
Source dataset
uspto-grants-2011_11
Patent number
US08058276B2

Reaction notes

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