Water → HCID 59299469, compound

HRID 2235289Notes

Reaction equation

HRID 2235289 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]([CH2:6][CH:7]2[CH2:11][CH2:10][N:9]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)[C:8]2=[O:18])=[C:4]([Cl:21])[CH:3]=1.[Br-].[CH:23]1([Zn+])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.O>C1COCC1.CN1C(=O)CCC1.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]>[Cl:21][C:4]1[CH:3]=[C:2]([CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH:20]=[CH:19][C:5]=1[CH2:6][CH:7]1[CH2:11][CH2:10][N:9]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[C:8]1=[O:18]

Participants

6

Reactant 3

HCID 962WaterHCID 116822063-(4-Bromo-2-chlorobenzyl)-1-cyclohexylpyrrolidin-2-oneHCID 178418970HCID 178418970, compound

Product 1

HCID 59299469HCID 59299469, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 22156051tetrahydrofuran N-methylpyrrolidinoneSolvent

Procedure

Dissolve 3-(4-bromo-2-chlorobenzyl)-1-cyclohexylpyrrolidin-2-one (Example 55) (0.20 g, 0.54 mmol) in THF/NMP (10 mL/10 mL) under N2. Add Pd(dppf)Cl2 (0.04 g, 0.054 mmol) and cyclohexylzinc(II) bromide (1.08 mL, 0.5 M in THF) with stiring. Heat the reaction mixture to reflux for 4 hours until LC-MS shows the starting material has gone. Cool the reaction to room temperature and add water (20 mL). Extract the aqueous with EtOAc (3×50 mL). Combine the organic layers and dry with Na2SO4, filter, concentrate and purify by flash column chromatography (silica gel, 10-50% of EtOAc-Hexane) to give 0.20 g (83%) of the title compound as a colorless oil: MS (APCI-pos mode) m/z (rel intensity) 374.3 (100), 376.3 (30).

Workup

  1. temperatureHeat the reaction mixture
  2. temperatureto reflux for 4 hours until LC-MS
  3. temperatureCool
  4. customthe reaction to room temperature
  5. extractionExtract the aqueous with EtOAc (3×50 mL)
  6. dry with materialCombine the organic layers and dry with Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. custompurify by flash column chromatography (silica gel, 10-50% of EtOAc-Hexane)

Sources & evidence

ORD record
ord-aa36a4385507434f886e5946eb653d21
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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