Acetic Acid → 4-{[5-(5,6-Difluoro-1H-indol-2-yl)-2-methoxy-phenylamino]-methyl}-benzoic acid methyl ester

HRID 25503Notes

Reaction equation

HRID 25503 reaction equation
[CH:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1)=O.[F:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][C:22]=1[F:23])[NH:19][C:18]([C:24]1[CH:25]=[CH:26][C:27]([O:31][CH3:32])=[C:28]([NH2:30])[CH:29]=1)=[CH:17]2.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH3:10][O:9][C:7](=[O:8])[C:6]1[CH:11]=[CH:12][C:3]([CH2:1][NH:30][C:28]2[CH:29]=[C:24]([C:18]3[NH:19][C:20]4[C:16]([CH:17]=3)=[CH:15][C:14]([F:13])=[C:22]([F:23])[CH:21]=4)[CH:25]=[CH:26][C:27]=2[O:31][CH3:32])=[CH:4][CH:5]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 15294Methyl 4-FormylbenzoateHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 99434395-(5,6-difluoro1H-indol-2-yl)-2-methoxy-phenylamine

Product 1

HCID 101805604-{[5-(5,6-Difluoro-1H-indol-2-yl)-2-methoxy-phenylamino]-methyl}-benzoic acid methyl esterYield 26.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl 4-formylbenzoate (0.21 g, 1.28 mmol) was added to a stirred mixture of 5-(5,6-difluoro-1H-indol-2-yl)-2-methoxy-phenylamine (0.34 g, 1.24 mmol) in methylene chloride (125 mL), followed by acetic acid (0.3 g, 3.33 mmol). The resulting mixture was stirred at room temperature for 1 hour. Sodium triacetoxyborohydride (0.3 g, 1.42 mmol) was added in one portion, and the resulting homogeneous solution stirred at room temperature for 4 days. Saturated aqueous sodium bicarbonate solution (100 mL) was added and the mixture stirred for 2 hours. The mixture was shaken, the organic layer separated, and dried over Na2SO4. The solvent was evaporated to give a brown gum. Recrystallization from methanol gave the product as off-white crystals (140 mg), mp 168-170° C.

Workup

  1. stirringthe resulting homogeneous solution stirred at room temperature for 4 days
  2. stirringthe mixture stirred for 2 hours
  3. stirringThe mixture was shaken
  4. customthe organic layer separated
  5. dry with materialdried over Na2SO4
  6. customThe solvent was evaporated
  7. customto give a brown gum
  8. customRecrystallization from methanol

Sources & evidence

ORD record
ord-ce84348b194c46e0a37af5ef56f97c3e
Source dataset
uspto-grants-2005_02
Patent number
US06858739B2

Reaction notes

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