Water → 4-[4-Chloro-3-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-2-fluoro-phenyl]-butyric acid ethyl ester

HRID 2235244Notes

Reaction equation

HRID 2235244 reaction equation
Br[C:2]1[C:3]([F:22])=[C:4]([C:18]([Cl:21])=[CH:19][CH:20]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][N:8]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[C:7]1=[O:17].[Br-].[CH2:24]([O:26][C:27](=[O:32])[CH2:28][CH2:29][CH2:30][Zn+])[CH3:25].O>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:24]([O:26][C:27](=[O:32])[CH2:28][CH2:29][CH2:30][C:2]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:4]([CH2:5][CH:6]2[CH2:10][CH2:9][N:8]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[C:7]2=[O:17])[C:3]=1[F:22])[CH3:25]

Participants

6

Reactant 3

HCID 962WaterHCID 116896233-(3-Bromo-6-chloro-2-fluoro-benzyl)-1-cyclohexyl-pyrrolidin-2-oneHCID 178471550HCID 178471550, compound

Product 1

HCID 592994384-[4-Chloro-3-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-2-fluoro-phenyl]-butyric acid ethyl esterYield 92%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve 3-(3-bromo-6-chloro-2-fluoro-benzyl)-1-cyclohexyl-pyrrolidin-2-one (Example 30) (1 g, 2.6 mmol) and Pd(dppf)Cl2 (80 mg, 0.1 mol) in THF (degassed, 40 mL) and add 4-ethoxy-4-oxo-butylzinc bromide (15 mL, 7.7 mmol, 0.5 M THF solution). Reflux the reaction for 3 hours. Add the reaction mixture into ice and water. Extract the mixture with ethyl acetate (100 mL). Wash the organic layer with brine (50 mL), dry with magnesium sulfate, filter and evaporate solvent under reduced pressure. Purify the residue by column chromatography using 10% EA/H to 30% EA/H to obtain the title compound (1 g, 92%) as yellow oil: Mass spectrum (ion spray): m/z=424.1 (M+H).

Workup

  1. temperatureReflux
  2. customthe reaction for 3 hours
  3. extractionExtract the mixture with ethyl acetate (100 mL)
  4. washWash the organic layer with brine (50 mL)
  5. dry with materialdry with magnesium sulfate
  6. filtrationfilter
  7. customevaporate solvent under reduced pressure
  8. customPurify the residue by column chromatography

Sources & evidence

ORD record
ord-be02a55be47d4a7695965be9a3e146c3
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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