Ethyl bromoacetate → [3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-yloxy]-acetic acid ethyl ester

HRID 2235296Notes

Reaction equation

HRID 2235296 reaction equation
[CH:1]1([N:7]2[CH2:11][CH2:10][CH:9]([CH2:12][C:13]3[C:18]([Cl:19])=[CH:17][C:16]([C:20]4[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=4)=[CH:15][C:14]=3[Cl:27])[C:8]2=[O:28])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32].[Na+].ClC1C=C(C2C=CC(C([O-])=O)=CC=2)C=CC=1CC1CCN(C2CCCCC2)C1=O>CN(C=O)C>[CH2:34]([O:33][C:31](=[O:32])[CH2:30][O:26][C:23]1[CH:24]=[CH:25][C:20]([C:16]2[CH:15]=[C:14]([Cl:27])[C:13]([CH2:12][CH:9]3[CH2:10][CH2:11][N:7]([CH:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)[C:8]3=[O:28])=[C:18]([Cl:19])[CH:17]=2)=[CH:21][CH:22]=1)[CH3:35]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 592993351-Cyclohexyl-3-(3,5-dichloro-4'-hydroxy-biphenyl-4-ylmethyl)-pyrrolidin-2-oneHCID 684693703'-Chloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-carboxylic acid sodium salt

Product 1

HCID 11569665[3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-yloxy]-acetic acid ethyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Combine 1-cyclohexyl-3-(3,5-dichloro-4′-hydroxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one (Preparation 52) (0.15 g, 0.36 mmol), ethyl bromoacetate (0.12 g, 0.718 mmol) and Cs2CO 3 (0.29 g, 0.89 mmol) in DMF (6 mL) and heat to 60° C. for 16 hours. Cool the reaction, extract with diethyl ether and water, dry the organic layer (Na2SO4) and then purify by normal phase chromatography (30 to 80% gradient of ethyl acetate in hexanes) to afford 159 mg (88%) of the title compound: LC-MS (ES+) m/z=exact mass calcd for C27H31Cl2NO4 503, found 504 and 506 (M+1 and M+3, 100%).

Workup

  1. temperatureCool
  2. customthe reaction
  3. extractionextract with diethyl ether and water
  4. dry with materialdry the organic layer (Na2SO4)
  5. custompurify by normal phase chromatography (30 to 80% gradient of ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2dd29a72ddd24f2a8aaf1732e5a6420d
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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