Cesium carbonate → 2-[3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-yloxy]-2-methyl-propionic acid ethyl ester

HRID 2235294Notes

Reaction equation

HRID 2235294 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[C:30]([CH3:37])([CH3:36])[C:31]([O:33][CH2:34][CH3:35])=[O:32].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH2:34]([O:33][C:31](=[O:32])[C: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)([CH3:37])[CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 592993351-Cyclohexyl-3-(3,5-dichloro-4'-hydroxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one

Product 1

HCID 116062232-[3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-yloxy]-2-methyl-propionic acid ethyl esterYield 104.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Combine 1-Cyclohexyl-3-(3,5-dichloro-4′-hydroxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one (prep 55) (0.15 g, 0.36 mmol), ethyl 2-bromoisobutyrate (0.28 g, 1.43 mmol) and Cs2CO3 (0.35 g, 1.07 mmol) in DMF (7 mL) and heat to 60° C. for 16 hours. Cool the reaction, extract with diethyl ether and water, dry (Na2SO4) and then purify by normal phase chromatography (30 to 80% gradient of ethyl acetate in hexanes) to afford 200 mg (100%) of the title compound: LC-MS (ES +) m/z=exact mass calcd for C29H35Cl2NO4 531, found 532 and 534 (M+1 and M+3, 100%).

Workup

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

Sources & evidence

ORD record
ord-8c7aa6d982004f33b64288b9ff6ab86c
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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