Cesium carbonate → HCID 67506447, compound

HRID 473807Notes

Reaction equation

HRID 473807 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][C:13](=[O:15])[CH2:12][CH2:11][N:10]2[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH:5]=[CH:6][C:7]=1[F:8].C(=O)([O-])[O-].[Cs+].[Cs+].C[Si](C)(C)[C:34]([F:37])([F:36])[F:35].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.CO.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][C:13]([OH:15])([C:34]([F:37])([F:36])[F:35])[CH2:12][CH2:11][N:10]2[C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 552549(Trifluoromethyl)trimethylsilaneHCID 67506327HCID 67506327, compound

Product 1

HCID 67506447HCID 67506447, compoundYield 96.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of benzyl 2-(3,4-difluorophenyl)-4-oxopiperidine-1-carboxylate (0.21 g, 0.60 mmol) (reagent preparation 20, step 2) in dimethylformamide (4.0 mL) at 0° C. was added cesium carbonate (0.30 g, 0.90 mmol), followed by the addition of trimethyl(trifluoromethyl)silane (0.35 mL, 2.40 mmol). The reaction mixture was stirred at room temperature for 12 hours then partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate then filtered and concentrated. To a solution of the residue in methanol was added potassium carbonate (0.16 g, 1.19 mmol) and the reaction mixture was stirred at room temperature for 24 hours. The mixture was diluted with ethyl acetate and washed with 1M aqueous hydrochloric acid, brine, dried over anhydrous magnesium sulfate then filtered and concentrated to give benzyl 2-(3,4-difluorophenyl)-4-hydroxy-4-(trifluoromethyl)piperidine-1-carboxylate (0.24 g, quantitative).

Workup

  1. customthen partitioned between ethyl acetate and water
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationthen filtered
  6. concentrationconcentrated
  7. stirringthe reaction mixture was stirred at room temperature for 24 hours
  8. washwashed with 1M aqueous hydrochloric acid, brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationthen filtered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-491b73eded8543ae9098bbba8efaba30
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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