Ethyl 2-(4-amino-2-fluorophenyl)acetate → Ethyl (4-{[(2-chloro-5-{[(3-chlorophenyl)methyl]oxy}phenyl)carbonyl]amino}-2-fluorophenyl)acetate

HRID 1879112

Reaction equation

HRID 1879112 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.Cl.CN(C)CCN=C=NCC.[NH2:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[C:34]([F:44])[CH:33]=1>ClCCl.CO>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)=[CH:7][C:3]=1[C:4]([NH:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[C:34]([F:44])[CH:33]=1)=[O:6]

Participants

6

Reactant 3

HCID 15840528Ethyl 2-(4-amino-2-fluorophenyl)acetateHCID 57494384N-[2-(dimethylamino)ethyl]-N'-ethylcarbodiimide hydrochlorideHCID 597600492-Chloro-5-{[(3-chlorophenyl)methyl]oxy}benzoic acid

Product 1

HCID 59163386Ethyl (4-{[(2-chloro-5-{[(3-chlorophenyl)methyl]oxy}phenyl)carbonyl]amino}-2-fluorophenyl)acetateYield 33%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-chloro-5-{[(3-chlorophenyl)methyl]oxy}benzoic acid (207 mg, 0.7 mmol) in dichloromethane (3 ml) was treated with N-[2-(dimethylamino)ethyl]-N′-ethylcarbodiimide hydrochloride (201 mg, 1.05 mmol, 1.5 eq) and stirred at room temperature for 30 minutes. A solution of ethyl (4-amino-2-fluorophenyl)acetate (207 mg, 1.05 mmol, 1.5 eq) in dichloromethane (2 ml) was added and the resulting mixture heated at 40° C. overnight. On cooling, the mixture was diluted with methanol and purified by SCX cartridge eluting with methanol to afford the title compound as a yellow oil (110 mg). MS (ES+) m/z 476 [M+H]+ (C24H2035Cl2FNO4). 1H-NMR (400 MHz, d6-DMSO) δ 1.19 (3H, t, J 7.2), 3.68 (2H, s), 4.09 (2H, q, J 7.2), 5.20 (2H, s), 7.15-7.68 (10H, m).

Workup

  1. temperaturethe resulting mixture heated at 40° C. overnight
  2. temperatureOn cooling
  3. custompurified by SCX cartridge
  4. washeluting with methanol

Sources & evidence

ORD record
ord-de727b0ead63478bb37214cd9fd71c6a
Source dataset
uspto-grants-2012_11
Patent number
US08314147B2

Linked notes

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