Dibromodifluoromethane → HCID 11608680, compound

HRID 252030Notes

Reaction equation

HRID 252030 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:19](Br)([F:21])[F:20].CN(P(N(C)C)(N(C)C)=O)C>C1COCC1.[Zn]>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14](=[C:19]([F:21])[F:20])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6382DibromodifluoromethaneHCID 12679Hexamethylphosphoramide2×HCID 643496Benzyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 11608680HCID 11608680, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-oxo-piperidine-1-carboxylic acid benzyl ester (0.50 g, 2.14 mmol, 1.0 eq.) in THF (20 mL) was added dibromodifluoromethane (0.90 mL, 4.5 eq.) at −30° C. followed by HMPA (1.75 mL, 4.5 eq.). The cooling bath was removed and the reaction mixture was swirled periodically. After 30 min, zinc dust (0.63 g, 4.5 eq.) and HMPA (80 μL 0.4 eq.) was added and the mixture was heated at reflux for 18 h. Upon cooling to room temperature, the residue was washed with diethyl ether several times. The combined ether washings were washed successively with saturated aqueous copper (II) sulphate, brine, dried over Na2SO4 and concentrated. The residue was purification by chromatography (20% EtOAc-hexanes) to afford 4-difluoromethylene-piperidine-1-carboxylic acid benzyl ester (0.32 g, 56%) as a colorless oil.

Workup

  1. customThe cooling bath was removed
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 18 h
  4. washthe residue was washed with diethyl ether several times
  5. washThe combined ether washings were washed successively with saturated aqueous copper (II) sulphate, brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. custompurification by chromatography (20% EtOAc-hexanes)

Sources & evidence

ORD record
ord-5f3e68e6871846ea8dc42b90748725da
Source dataset
uspto-grants-2011_01
Patent number
US07868002B2

Reaction notes

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