3-(Trifluoromethyl)aniline → HCID 67080778, compound

HRID 510743Notes

Reaction equation

HRID 510743 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=1)[O:9][CH2:8][CH2:7][CH:6]2[C:23]([O:25][CH3:26])=[O:24])#[N:2].C(Cl)(=O)C(Cl)=O.[F:33][C:34]([F:43])([F:42])[C:35]1[CH:36]=[C:37]([CH:39]=[CH:40][CH:41]=1)[NH2:38].C(N(CC)CC)C>ClCCl.CN(C)C=O.C(OCC)(=O)C>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:15]=[CH:16][C:17]([C:18](=[O:19])[NH:38][C:37]3[CH:39]=[CH:40][CH:41]=[C:35]([C:34]([F:33])([F:42])[F:43])[CH:36]=3)=[CH:21][CH:22]=1)[O:9][CH2:8][CH2:7][CH:6]2[C:23]([O:25][CH3:26])=[O:24])#[N:2]

Participants

8

Reactant 4

HCID 73753-(Trifluoromethyl)anilineHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 462211084-(6-Cyano-4-(methoxycarbonyl)-chroman-7-yloxy)benzoic acid

Product 1

HCID 67080778HCID 67080778, compoundYield 27%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(6-cyano-4-(methoxycarbonyl)chroman-7-yloxy)benzoic acid (0.050 g, 0.1415 mmol) in dichloromethane (0.7 ml) and N,N-dimethylformamide (1 drop) was added oxalyl dichloride (0.01358 ml, 0.1557 mmol), and the reaction was stirred at ambient temperature for 30 minutes. 3-(Trifluoromethyl)aniline (0.01944 ml, 0.1557 mmol) and triethylamine (0.04339 ml, 0.3113 mmol) were added, and the reaction was stirred at ambient temperature for 3 days. The reaction mixture was diluted with ethyl acetate and washed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was diluted with dichloromethane and stirred with excess amine-3 functionalized silica gel for 30 minutes, then filtered and concentrated. The crude material was purified by preparative thin layer chromatography eluting with 25% EtOAc in hexanes to yield 19 mg of the title compound (27% yield).

Workup

  1. stirringthe reaction was stirred at ambient temperature for 3 days
  2. washwashed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe residue was diluted with dichloromethane
  7. stirringstirred with excess amine-3 functionalized silica gel for 30 minutes
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by preparative thin layer chromatography
  11. washeluting with 25% EtOAc in hexanes

Sources & evidence

ORD record
ord-074669fe075a434ba185c241749a7509
Source dataset
uspto-grants-2015_08
Patent number
US09096567B2

Reaction notes

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