1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(2-{3-Dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-2-carbonyl)amino]phenoxy}acetoxymethyl)-2-phenylmalonic acid diethyl ester

HRID 2114182Notes

Reaction equation

HRID 2114182 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[C:5]([CH2:17][OH:18])([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].[CH3:20][N:21]([CH3:54])[C:22]([C:24]1[CH:25]=[C:26]([CH:32]=[CH:33][C:34]=1[NH:35][C:36]([C:38]1[C:39]([C:44]2[CH:49]=[CH:48][C:47]([C:50]([F:53])([F:52])[F:51])=[CH:46][CH:45]=2)=[CH:40][CH:41]=[CH:42][CH:43]=1)=[O:37])[O:27][CH2:28][C:29](O)=[O:30])=[O:23].CCN=C=NCCCN(C)C>CN(C)C1C=CN=CC=1.CC(C)=O>[CH2:9]([O:8][C:6](=[O:7])[C:5]([CH2:17][O:18][C:29](=[O:30])[CH2:28][O:27][C:26]1[CH:32]=[CH:33][C:34]([NH:35][C:36]([C:38]2[C:39]([C:44]3[CH:49]=[CH:48][C:47]([C:50]([F:53])([F:51])[F:52])=[CH:46][CH:45]=3)=[CH:40][CH:41]=[CH:42][CH:43]=2)=[O:37])=[C:24]([C:22](=[O:23])[N:21]([CH3:20])[CH3:54])[CH:25]=1)([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:4]([O:3][CH2:1][CH3:2])=[O:19])[CH3:10]

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 22236963Diethyl 2-(hydroxymethyl)-2-phenylmalonateHCID 23130252{3-Dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-2-carbonyl)amino]phenoxy}acetic acid

Product 1

HCID 114115822-(2-{3-Dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-2-carbonyl)amino]phenoxy}acetoxymethyl)-2-phenylmalonic acid diethyl esterYield 50%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 180AcetoneSolvent

Procedure

4-Dimethylaminopyridine (53 mg), 2-hydroxymethyl-2-phenylmalonic acid diethyl ester (116 mg) and {3-dimethylcarbamoyl-4-[(4′-trifluoromethylbiphenyl-2-carbonyl)amino]phenoxy}acetic acid (176 mg) were dissolved in acetone (5 mL), and to the solution was added WSC (104 mg). The mixture was stirred at room temperature for 3 hours and then concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:1) to give 2-(2-{3-dimethylcarbamoyl-4-[(4′-trifluoromethylbiphenyl-2-carbonyl)amino]phenoxy}acetoxymethyl)-2-phenylmalonic acid diethyl ester (133 mg) as a colorless solid (m.p. 132-138° C.).

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:1)

Sources & evidence

ORD record
ord-b1971e0eba7e45ef84237b83481160da
Source dataset
uspto-grants-2008_10
Patent number
US07432392B2

Reaction notes

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