Sodium Carbonate → 3-(2,6-Dichloro-4-pyridin-3-yl-benzyl)-1-(4,4-difluoro-cyclohexyl)-pyrrolidin-2-one

HRID 1672743Notes

Reaction equation

HRID 1672743 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[C:6]([Cl:23])[C:7]=1[CH2:8][CH:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:19][CH2:18][C:17]([F:21])([F:20])[CH2:16][CH2:15]2)[C:10]1=[O:22].[N:32]1[CH:37]=[CH:36][CH:35]=[C:34](B(O)O)[CH:33]=1.C([O-])([O-])=O.[Na+].[Na+]>C(COC)OC.C([O-])(O)=O.[Na+].CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:34]2[CH:33]=[N:32][CH:37]=[CH:36][CH:35]=2)[CH:5]=[C:6]([Cl:23])[C:7]=1[CH2:8][CH:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:19][CH2:18][C:17]([F:20])([F:21])[CH2:16][CH2:15]2)[C:10]1=[O:22]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 57878605Trifluoro-methanesulfonic acid 3,5-dichloro-4-[1-(4,4-difluoro-cyclohexyl)-2-oxo-pyrrolidin-3-ylmethyl]-phenyl ester

Product 1

HCID 578785963-(2,6-Dichloro-4-pyridin-3-yl-benzyl)-1-(4,4-difluoro-cyclohexyl)-pyrrolidin-2-one

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Heat a solution of trifluoro-methanesulfonic acid 3,5-dichloro-4-[1-(4,4-difluoro-cyclohexyl)-2-oxo-pyrrolidin-3-ylmethyl]-phenyl ester (Preparation 33) (0.585 g, 1.15 mmol), pyridine-3-boronic acid (0.283 g, 2.30 mmol), Pd(PPh3)4 (133 mg), 11.5 mL of 0.1 M Na2CO3 aq solution in 11.5 mL of dimethoxy ethane at 80° C. for 24 hr. Cool the mixture to room temp and dilute with 20 mL of 1N NaHCO3. Dilute the mixture with 20 mL of EtOAc. Wash the organic layer with water, then brine, and dry over Na2SO4, filter and concentrate. Purify the crude material by chromatography to afford the title compound: mass spectrum (m/z): 439 (M+1).

Workup

  1. washWash the organic layer with water
  2. dry with materialbrine, and dry over Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate
  5. customPurify the crude material by chromatography

Sources & evidence

ORD record
ord-02b3eaa3d155473c9c714eb6f08fdfd1
Source dataset
uspto-grants-2011_08
Patent number
US07998999B2

Reaction notes

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