Citric Acid → n-Cbz-3-hydroxypiperidine

HRID 409605Notes

Reaction equation

HRID 409605 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3]1.C(N(CC)CC)C.[CH2:15]([O:22][C:23](Cl)=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl.C(Cl)(Cl)Cl>[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:23]([O:22][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:24])[CH2:3]1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 232933-Hydroxypiperidine

Product 1

HCID 561665n-Cbz-3-hydroxypiperidine

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a mixed solution containing 33.5 g of 3-hydroxypiperidine and 62.7 ml of triethylamine dissolved in 250 ml of methylene chloride was added dropwise a solution of 55.7 ml of benzyloxycarbonyl chloride in 150 ml of methylene chloride, and the mixture was stirred at room temperature for 16 hours. To the reaction mixture were added a saturated aqueous citric acid and chloroform, the mixture was stirred and the liquids were separated. The organic layer was dried, the solvent was evaporated, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=4→0:1) to obtain 75.5 g of benzyl 3-hydroxypiperidine-1-carboxylate.

Workup

  1. stirringthe mixture was stirred
  2. customthe liquids were separated
  3. customThe organic layer was dried
  4. customthe solvent was evaporated
  5. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4→0:1)

Sources & evidence

ORD record
ord-de3d0d6896e348779a658ddf660aee00
Source dataset
uspto-grants-2014_06
Patent number
US08759387B2

Reaction notes

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