Hydrochloric Acid → HCID 23079679, compound

HRID 2112762Notes

Reaction equation

HRID 2112762 reaction equation
Br[C:2]([F:9])([F:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[O:10]=[C:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.C(OCC)(=O)C.Cl>O1CCCC1.[Zn]>[CH2:6]([O:5][C:3]([C:2]([F:9])([F:8])[C:11]1([OH:10])[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:15][CH2:16]1)=[O:4])[CH3:7]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 69585Ethyl bromodifluoroacetateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 23079679HCID 23079679, compound

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Powdered zinc (2.82 g, 0.043 mol) was suspended in tetrahydrofuran (50.0 mL) under flow of argon gas, and the suspension was mixed with ethyl bromodifluoroacetate (7.31 g, 0.036 mol) at room temperature, followed by stirring under reflux for five minutes. The mixture was further mixed with a solution of tert-butyl 4-oxopiperidinecarboxylate in tetrahydrofuran (3.00 mol/L, 10.0 mL, 0.030 mol), followed by stirring under reflux for two hours. After checking the completion of the reaction by thin layer chromatography, the reaction mixture was mixed with ethyl acetate and diluted hydrochloric acid (1.00 mol/L), followed by separation. The organic layer was sequentially washed with a saturated aqueous sodium bicarbonate solution and brine, was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane: chloroform=1:9) and thereby yielded tert-butyl 4-(ethoxycarbonyldifluoromethyl)-4-hydroxy-piperidinecarboxylate (7.39 g, 76%).

Workup

  1. temperatureunder reflux for five minutes
  2. stirringby stirring
  3. temperatureunder reflux for two hours
  4. customthe completion of the reaction by thin layer chromatography
  5. customfollowed by separation
  6. washThe organic layer was sequentially washed with a saturated aqueous sodium bicarbonate solution and brine
  7. dry with materialwas dried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane: chloroform=1:9)

Sources & evidence

ORD record
ord-feec1d76fd594d4d87e7e01ae0c11ce3
Source dataset
uspto-grants-2009_04
Patent number
US07524852B2

Reaction notes

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