Benzyl chloroformate → Phenylmethyl 3-(5-hydroxypentyl)-1-piperidinecarboxylate

HRID 2403835Notes

Reaction equation

HRID 2403835 reaction equation
C([O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][NH:12][CH2:11]1)(=O)C.[OH-].[K+].Cl[C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]>C1COCC1.O>[OH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:11]1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 14797Potassium HydroxideHCID 671812975-(3-Piperidinyl)-1-pentanol acetate

Product 1

HCID 58306078Phenylmethyl 3-(5-hydroxypentyl)-1-piperidinecarboxylateYield 66.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 5-(3-piperidinyl)-1-pentanol acetate (7.37 g, 31.9 mmol) in THF (50 ml) was added a solution of potassium hydroxide (5.36 g, 96 mmol) in water (30 ml) and the mixture was stirred in an ice-water bath. To this was added a solution of benzyl chloroformate (5.00 ml, 35.0 mmol) in THF (25 mL) dropwise over a period of 40 mins. After stirring in the cold bath for 30 mins., the mixture was allowed to warm to rt and stirred for 5 hours. The organic solvent was removed by evaporation in vacuo and the aqueous phase was diluted further with water (75 ml) and extracted with EtOAc (3×100 ml). The combined organic extracts was washed with saturated NaCl solution (100 ml), separated, dried (Na2SO4), filtered the solvent evaporated in vacuo and the residue was purified by column chromatography. The sample was loaded in dichloromethane and purified on silica (Si) 2×100 g cartridges using a gradient of 0-100% ethyl acetate in cyclohexane over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a colourless oil (6.50 g).

Workup

  1. stirringAfter stirring in the cold bath for 30 mins
  2. stirringstirred for 5 hours
  3. customThe organic solvent was removed by evaporation in vacuo
  4. additionthe aqueous phase was diluted further with water (75 ml)
  5. extractionextracted with EtOAc (3×100 ml)
  6. washThe combined organic extracts was washed with saturated NaCl solution (100 ml)
  7. customseparated
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered the solvent
  10. customevaporated in vacuo
  11. customthe residue was purified by column chromatography
  12. custompurified on silica (Si) 2×100 g cartridges
  13. customover 40 mins
  14. customevaporated in vacuo

Sources & evidence

ORD record
ord-d8a2f9ab496d4183aff8ca214b6fd632
Source dataset
uspto-grants-2014_08
Patent number
US08802684B2

Reaction notes

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