Potassium Carbonate → (R)-2,2-difluoro-hexahydro-5,5-dimethylindolizin-7(1H)-one

HRID 1754405Notes

Reaction equation

HRID 1754405 reaction equation
[F:1][C:2]1([F:14])[CH2:6][NH:5][C@H:4]([CH2:7][C:8](=[O:13])[CH:9]=[C:10]([CH3:12])[CH3:11])[CH2:3]1.C([O-])([O-])=O.[K+].[K+]>CO>[F:14][C:2]1([F:1])[CH2:6][N:5]2[C@H:4]([CH2:7][C:8](=[O:13])[CH2:9][C:10]2([CH3:11])[CH3:12])[CH2:3]1

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 867044601-((R)-4,4-difluoropyrrolidin-2-yl)-4-methylpent-3-en-2-one

Product 1

HCID 86704459(R)-2,2-difluoro-hexahydro-5,5-dimethylindolizin-7(1H)-oneYield 69%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A MeOH (350 ml) solution of 1-((R)-4,4-difluoropyrrolidin-2-yl)-4-methylpent-3-en-2-one and K2CO3 (2.5 g, 18 mmol) was stirred at 40° C. for 15 hours, the reaction went to completion as monitored by LC-MS. Solvent was removed in vacuo, remaining material was suspended in CH2Cl2, solid was filtered off, filtrate was collected and solvent was removed in vacuo. Product was purified by silica gel chromatography (Hexane/EtOAc, linear gradient from 100:0 to 80:20). Compound (R)-2,2-difluoro-hexahydro-5,5-dimethylindolizin-7(1H)-one was obtained as a light yellow solid: 637.4 mg (69% yield over 3 steps).

Workup

  1. customSolvent was removed in vacuo
  2. filtrationsolid was filtered off
  3. customfiltrate was collected
  4. customsolvent was removed in vacuo
  5. customProduct was purified by silica gel chromatography (Hexane/EtOAc, linear gradient from 100:0 to 80:20)

Sources & evidence

ORD record
ord-ada72bd7b8aa454da025c8d9e3671df5
Source dataset
uspto-grants-2015_10
Patent number
US09169249B2

Reaction notes

Loading…