Chlorotrimethylsilane → Benzyl 3-fluoro-4-oxopiperidine-1-carboxylate

HRID 2375458Notes

Reaction equation

HRID 2375458 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C[Si](Cl)(C)C.[B-](F)(F)(F)[F:31].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>CN(C=O)C>[F:31][CH:13]1[C:14](=[O:17])[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12]1

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 2724933Selectfluor

Product 1

HCID 42609253Benzyl 3-fluoro-4-oxopiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 10.0 g (43 mmol) of benzyl-4-oxo-1-piperidinecarboxylate in 25 mL of DMF was added 14.3 mL (103 mmol) of triethylamine and then 6.53 mL (52 mmol) of TMSCl. The reaction was heated at 80° C. overnight, cooled to room temperature, and then dumped into hexanes in a separatory funnel. The mixture was partitioned with saturated aqueous NaHCO3, separated, washed with brine, dried over MgSO4 and concentrated by rotary evaporation. The residue was dissolved in 500 mL of CH3CN and treated with 16.7 g (47 mmol) of Selectfluor. After 90 min the reaction was concentrated to about half the original volume, partitioned between EtOAc and brine, separated, dried over MgSO4, filtered, and concentrated by rotary evaporation. The residue was loaded onto a silica gel column and eluted with EtOAc/hexanes to provide 2-2 as a colorless oil.

Workup

  1. temperaturecooled to room temperature
  2. customThe mixture was partitioned with saturated aqueous NaHCO3
  3. customseparated
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated by rotary evaporation
  7. dissolutionThe residue was dissolved in 500 mL of CH3CN
  8. concentrationAfter 90 min the reaction was concentrated to about half the original volume
  9. custompartitioned between EtOAc and brine
  10. customseparated
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated by rotary evaporation
  14. washeluted with EtOAc/hexanes

Sources & evidence

ORD record
ord-5ed7c9c63a4e4060a7b8cd1035c93457
Source dataset
uspto-grants-2008_12
Patent number
US07465746B2

Reaction notes

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