4-Fluoro-3-(trifluoromethyl)aniline → HCID 178432351, compound

HRID 1898452Notes

Reaction equation

HRID 1898452 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]1[NH:22][C:21]2[C:16]3[N:17]=[C:18]([CH3:20])[O:19][C:15]=3[C:14]([C:23]([O:25]C)=O)=[CH:13][C:12]=2[N:11]=1.[F:27][C:28]1[CH:34]=[CH:33][C:31]([NH2:32])=[CH:30][C:29]=1[C:35]([F:38])([F:37])[F:36].C[Al](C)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]1[NH:22][C:21]2[C:16]3[N:17]=[C:18]([CH3:20])[O:19][C:15]=3[C:14]([C:23]([NH:32][C:31]3[CH:33]=[CH:34][C:28]([F:27])=[C:29]([C:35]([F:38])([F:36])[F:37])[CH:30]=3)=[O:25])=[CH:13][C:12]=2[N:11]=1

Participants

5

Reactant 3

HCID 753774-Fluoro-3-(trifluoromethyl)anilineHCID 16682925TrimethylaluminumHCID 178496996HCID 178496996, compound

Product 1

HCID 178432351HCID 178432351, compoundYield 19.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Under inert atmosphere to a solution of methyl 7-[(2-chloro-6-fluorophenyl)amino]-2-methyl-8H-imidazo[4,5-e][1,3]benzoxazole-4-carboxylate (Step-3 of Intermediate-56, 0.100 g, 0.297 mmol) in dry toluene was added 4-fluoro-3-trifluoromethyl aniline (0.080 g, 0.446 mmol) and trimethyl aluminium (2.0 M solution in toluene) (0.037 g, 0.516 mmol). The reaction mixture was refluxed for 1 h. The reaction mass was quenched in water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated. The obtained crude was purified by column chromatography on basic alumina eluting with 0.75-1% DCM: MeOH to afford 0.030 g of the desired product. 1HNMR (DMSO-d6): δ 2.65 (s, 3H), 7.40-7.57 (m, 4H), 7.65 (s, 1H), 8.06 (m, 1H), 8.30 (s, 1H), 9.37 (s, 1H), 10.40 (s, 1H), 11.68 (s, 1H); MS [M+H]+: 522.14.

Workup

  1. temperatureThe reaction mixture was refluxed for 1 h
  2. customThe reaction mass was quenched in water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  5. concentrationconcentrated
  6. customThe obtained crude
  7. customwas purified by column chromatography on basic alumina eluting with 0.75-1% DCM

Sources & evidence

ORD record
ord-36c04dde7cb8474da5a1a39b92b94940
Source dataset
uspto-grants-2013_08
Patent number
US08519149B2

Reaction notes

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