Benzyl Alcohol → tert-Butyl 3-{[(benzyloxy)carbonyl]amino}piperidine-1-carboxylate

HRID 1934686Notes

Reaction equation

HRID 1934686 reaction equation
C1(P([N:15]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[C:18]([O:22][C:23]([N:25]1[CH2:33][CH2:32][CH2:31][CH:27](C(O)=O)[CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].[CH2:34]([OH:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.Cl.C([O:46][CH2:47]C)(=O)C>C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH2:34]([O:41][C:47]([NH:15][CH:27]1[CH2:31][CH2:32][CH2:33][N:25]([C:23]([O:22][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:24])[CH2:26]1)=[O:46])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

8

Reactant 5

HCID 244Benzyl AlcoholHCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 199401P,P-Diphenylphosphinic azideHCID 27356471-((Tert-butoxy)carbonyl)piperidine-3-carboxylic acid

Product 1

HCID 22467587tert-Butyl 3-{[(benzyloxy)carbonyl]amino}piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

Diphenylphosphorylazide (2.60 g) was added dropwise to a mixture of N-(tert-butoxycarbonyl)nipecotic acid (2.06 g) and triethylamine (1.00 g) in toluene (20 mL). The reaction mixture was warmed in an oil bath over 10 minutes at 100° C. Stirring was continued for 2 hours at 100° C., then the reaction vessel was taken out from the oil bath. After reflux was ceased, benzyl alcohol (1.07 g) was added to the reaction mixture. The mixture was stirred for 3 hours at 100° C., and then poured into a mixture of 3.6% hydrochloric acid, ice and ethyl acetate. The separated organic layer was washed with brine, an aqueous saturated sodium bicarbonate solution and brine, successively. The resultant was dried over magnesium sulfate and concentrated in vacuo. The residue was purified by a silica gel column chromatography eluting with 30% ethyl acetate in hexane to give 3-(benzyloxycarbonylamino)-1-tert-butoxycarbonylpiperidine (2.66 g) as an oil.

Workup

  1. temperatureAfter reflux
  2. stirringThe mixture was stirred for 3 hours at 100° C.
  3. washThe separated organic layer was washed with brine
  4. dry with materialThe resultant was dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by a silica gel column chromatography
  7. washeluting with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-5bf39256074e4fada84fb182fd843a6c
Source dataset
uspto-grants-2002_05
Patent number
US06384080B1

Reaction notes

Loading…