Water → n-Cbz-3-hydroxypiperidine

HRID 581721Notes

Reaction equation

HRID 581721 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3]1.O.Cl[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11].[OH-].[Na+]>C(OCC)(=O)C>[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 232933-Hydroxypiperidine

Product 1

HCID 561665n-Cbz-3-hydroxypiperidine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a 1-liter 3-necked round bottom flask, equipped with mechanical stirrer and two addition funnels, is added 30 g (0.2966 mole) of 3-hydroxypiperidine and 300 ml of water. The resulting solution is stirred and is cooled to ~0° C. with ice-salt bath. At this point the benzyl chloroformate (51 ml, 0.356 mole) is added dropwise from one funnel and the 2N NaOH (178 ml) from the other funnel (at a slightly faster rate) during which time the temp. is maintained at ~0° C. After addition is complete, the mixture is stirred in the cold for 2 hr, then overnight at ambient temp. After this time an oily residue separates from the reaction solution. Ethyl acetate is added (250 ml) to the reaction and is stirred for 1/2 hr. The phases are separated and the aqueous phase is extracted once more with EtOAc (250 ml). All organic phases are combined, washed with 1×150 ml saturated NaHCO3, 1×150 ml H2O, 1×150 ml 10% HCl, 1×150 ml H2O and dried overMgSO4. The mixture is filtered and concentrated on a roto-evap under reduced pressure, to yield a viscous oil, which is stored under vacuum to remove any residual solvents as, 3-Hydroxy-1-piperidinecarboxylic Acid, Phenylmethyl Ester, a clear oil.

Workup

  1. customTo a 1-liter 3-necked round bottom flask, equipped with mechanical stirrer
  2. additiontwo addition funnels
  3. temperatureis cooled to ~0° C. with ice-salt bath
  4. temperatureis maintained at ~0° C
  5. additionAfter addition
  6. stirringthe mixture is stirred in the cold for 2 hr
  7. customovernight
  8. customat ambient temp
  9. customto the reaction
  10. stirringis stirred for 1/2 hr
  11. customThe phases are separated
  12. extractionthe aqueous phase is extracted once more with EtOAc (250 ml)
  13. washwashed with 1×150 ml saturated NaHCO3, 1×150 ml H2O, 1×150 ml 10% HCl, 1×150 ml H2O
  14. customdried overMgSO4
  15. filtrationThe mixture is filtered
  16. concentrationconcentrated on a roto-evap under reduced pressure
  17. customto yield a viscous oil, which
  18. customto remove any residual solvents as, 3-Hydroxy-1-piperidinecarboxylic Acid, Phenylmethyl Ester

Sources & evidence

ORD record
ord-1c710c68403c4128b8a73a9107cc2873
Source dataset
uspto-grants-1999_07
Patent number
US05922703

Reaction notes

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