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

HRID 1879113

Reaction equation

HRID 1879113 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.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[NH2:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])=[C:36]([F:46])[C:35]=1[Cl:47]>ClCCl.CN(C=O)C.C(#N)C>[Cl:47][C:35]1[C:36]([F:46])=[C:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH:38]=[CH:39][C:34]=1[NH:33][C:4]([C:3]1[CH:7]=[C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[CH:9]=[CH:10][C:2]=1[Cl:1])=[O:6]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 59163335Ethyl (4-amino-3-chloro-2-fluorophenyl)acetateHCID 597600492-Chloro-5-{[(3-chlorophenyl)methyl]oxy}benzoic acid

Product 1

HCID 59163365Ethyl (3-chloro-4-{[(2-chloro-5-{[(3-chlorophenyl)methyl]oxy}phenyl)carbonyl]amino}-2-fluorophenyl)acetateYield 32.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-chloro-5-{[(3-chlorophenyl)methyl]oxy}benzoic acid (200 mg, 0.67 mmol) in dichloromethane (3 ml) was treated with oxalyl chloride (90 ul, 1.0 mmol) and DMF (1 drop). Effervescence was observed and the mixture was stirred at room temperature for 30 minutes. The solvent was then evaporated in vacuo and azeotroped with toluene. The resulting solid was dissolved in dichloromethane (3 ml) and treated with triethylamine (140 ul, 1.0 mmol) and a solution of ethyl (4-amino-3-chloro-2-fluorophenyl)acetate (230 mg, 1.0 mmol) in dichloromethane (2 ml). The mixture was stirred at room temperature for 2 hours. The mixture was then diluted with acetonitrile and purified by SCX cartridge eluting with acetonitrile. Fractions combined and evaporated, residue purified by MDAP to give the title compound as a white solid (110 mg). MS (ES+) m/z 510 [M+H]+ (C24H1935Cl3FNO4). 1H-NMR (400 MHz, d6-DMSO) δ 1.20 (3H, t, J 7.2), 3.81 (2H, s), 4.12 (2H, q, J 7.2), 5.20 (2H, s), 7.16-7.55 (9H, m).

Workup

  1. customThe solvent was then evaporated in vacuo
  2. customazeotroped with toluene
  3. dissolutionThe resulting solid was dissolved in dichloromethane (3 ml)
  4. stirringThe mixture was stirred at room temperature for 2 hours
  5. custompurified by SCX cartridge
  6. washeluting with acetonitrile
  7. customevaporated
  8. customresidue purified by MDAP

Sources & evidence

ORD record
ord-0e63bfbbd08547d4bf830891d0501af1
Source dataset
uspto-grants-2012_11
Patent number
US08314147B2

Linked notes

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