Tert-Butylamine → 4-Amino-2-(2,4-dichlorophenylamino)-3-fluoro-5-isopropenyl-benzoic acid methyl ester

HRID 500561Notes

Reaction equation

HRID 500561 reaction equation
[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[C:8](Br)[C:7]([NH2:11])=[C:6]([F:12])[C:5]=1[NH:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[Cl:21].[C:23](N)(C)([CH3:25])[CH3:24]>C(O)(C)C.O.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[C:8]([C:23]([CH3:25])=[CH2:24])[C:7]([NH2:11])=[C:6]([F:12])[C:5]=1[NH:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[Cl:21]

Participants

5

Reactant 2

HCID 6385Tert-ButylamineHCID 865986354-Amino-5-bromo-2-(2,4-dichlorophenylamino)-3-fluorobenzoic acid methyl ester

Product 1

HCID 865986374-Amino-2-(2,4-dichlorophenylamino)-3-fluoro-5-isopropenyl-benzoic acid methyl esterYield 49.5%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21889133Propan-2-ol--water (1/1)Solvent

Procedure

A mixture of 4-amino-5-bromo-2-(2,4-dichlorophenylamino)-3-fluorobenzoic acid methyl ester (502 mg, 1.23 mmol), potassium isopropenyl trifluoroborate (218 mg, 1.47 mmol, Org. Lett. 2002, 4, 107), PdCl2(dppf)CH2Cl2 (101 mg, 0.122 mmol), and t-BuNH2 (0.39 mL, 3.67 mmol) in i-PrOH-H2O (2:1, 12 mL) was refluxed for 16 hours. The reaction mixture was diluted with EtOAc, washed with water, dried over MgSO4, filtered, and concentrated in vacuo to give the crude material which was purified by silica gel flash column chromatography (20% CH2Cl2 in hexanes) to give the desired product (225 mg, 49%).

Workup

  1. temperaturewas refluxed for 16 hours
  2. washwashed with water
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give the crude material which
  7. customwas purified by silica gel flash column chromatography (20% CH2Cl2 in hexanes)

Sources & evidence

ORD record
ord-a54a1335cc2c41c58d76efde86debdbe
Source dataset
uspto-grants-2010_08
Patent number
US07772234B2

Reaction notes

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