Acetic Acid → Tert-butyl 4-cyclohexyl-4-hydroxypiperidine-1-carboxylate

HRID 1816357Notes

Reaction equation

HRID 1816357 reaction equation
[Cl-].[Ce+3].[Cl-].[Cl-].[CH:5]1([Mg]Cl)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.[O:13]=[C:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.C(O)(=O)C>C1COCC1>[CH:5]1([C:14]2([OH:13])[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:18][CH2:19]2)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24636Cerium(III) chlorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178478990HCID 178478990, compound

Product 1

HCID 22492872Tert-butyl 4-cyclohexyl-4-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Anhydrous cerium(III) chloride (10.0 g) was added to THF (100 ml) with stirring under ice-cooling and a mixture was stirred at ambient temperature overnight and then cooled in an ice bath. A solution of cyclohexyl magnesium chloride (2M solution in diethyl ether) (20.3 ml) was dropwise added to the mixture with stirring on ice bath (keeping the temperature below 6° C.). To the mixture was added dropwise a solution of tert-butyl 4-oxo-1-piperidinecarboxylate (5.38 g) in THF (25 ml) and the mixture was stirred at 0-6° C. for 1 hour. 10% aqueous acetic acid (100 ml) was added to the reaction mixture and extracted twice with ethyl acetate (100 ml). The extracts were collected, washed with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated in vacuo. The resulting residue was chromatographed on silica gel (400 ml) eluting with a mixture of n-hexane and ethyl acetate (2:1 v/v). The fractions containing the desired compound were collected and evaporated under reduced pressure to give tert-butyl 4-cyclohexyl-4-hydroxy-1-piperidinecarboxylate (7.27 g).

Workup

  1. temperaturecooling
  2. stirringa mixture was stirred at ambient temperature overnight
  3. temperaturecooled in an ice bath
  4. stirringwith stirring on ice bath (
  5. customthe temperature below 6° C.
  6. stirringthe mixture was stirred at 0-6° C. for 1 hour
  7. extractionextracted twice with ethyl acetate (100 ml)
  8. customThe extracts were collected
  9. washwashed with saturated aqueous sodium chloride
  10. dry with materialdried over magnesium sulfate
  11. customevaporated in vacuo
  12. customThe resulting residue was chromatographed on silica gel (400 ml)
  13. washeluting with a mixture of n-hexane and ethyl acetate (2:1 v/v)
  14. additionThe fractions containing the desired compound
  15. customwere collected
  16. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-39199973b988483a8c1ede71bd1a708a
Source dataset
uspto-grants-2005_04
Patent number
US06884774B2

Reaction notes

Loading…