Methyl 4-aminobenzoate → Methyl 4-[[2-fluoro-4,6-bis(trifluoromethyl)benzoyl]amino]benzoate

HRID 1484193Notes

Reaction equation

HRID 1484193 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[F:21][C:22]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[C:23]=1[C:24](Cl)=[O:25]>CN(C=O)C.ClCCl.C(OCC)(=O)C>[F:21][C:22]1[CH:30]=[C:29]([C:31]([F:33])([F:34])[F:32])[CH:28]=[C:27]([C:35]([F:36])([F:37])[F:38])[C:23]=1[C:24]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=1)=[O:25]

Participants

7

Reactant 3

HCID 12082Methyl 4-aminobenzoateHCID 81531DiisopropylethylamineHCID 467375822-Fluoro-4,6-bis(trifluoromethyl)benzoyl chloride

Product 1

HCID 90314675Methyl 4-[[2-fluoro-4,6-bis(trifluoromethyl)benzoyl]amino]benzoateYield 33.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 4-aminobenzoate (514.6 mg, 3.40 mmol) and di-isopropylethyl amine (1.77 mL, 10.18 mmol) in DMF (10 mL) at 0° C. was added a solution of 2-fluoro-4,6-bis(trifluoromethyl)benzoyl chloride (1 g, 3.39 mmol) in dichloromethane. The reaction was complete after 10 min. The reaction mixture was diluted with ethyl acetate and washed with water (2×200 mL), 1 N HCl (2×50 mL), and brine then dried over Na2SO4, filtered and concentrated. Silica gel chromatography using a gradient of ethyl acetate/hexane (0-100%) provided methyl 4-[[2-fluoro-4,6-bis(trifluoromethyl)benzoyl]amino]benzoate (459 mg, 33%) as an off-white solid. ESI-MS m/z calc. 409.05. found 410.3 (M+1)+; Retention time: 1.86 minutes. 1H NMR (400 MHz, DMSO-d6) δ 11.22 (s, 1H), 8.36 (s, 1H), 7.62-7.57 (m, 2H), 7.56-7.51 (m, 2H), 7.51-7.46 (m, 1H), 3.42 (s, 3H) ppm.

Workup

  1. washwashed with water (2×200 mL), 1 N HCl (2×50 mL), and brine
  2. dry with materialthen dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-54a7463b0e624057a8bdaf34efc0e122
Source dataset
uspto-grants-2016_08
Patent number
US09421196B2

Reaction notes

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