1-((Phenylmethoxy)carbonyl)-3-piperidinebutanoic acid → Phenylmethyl 3-(4-hydroxybutyl)-1-piperidinecarboxylate

HRID 1044888Notes

Reaction equation

HRID 1044888 reaction equation
[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:16][CH2:15][CH2:14][CH:13]([CH2:17][CH2:18][CH2:19][C:20](O)=[O:21])[CH2:12]2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C1COCC1>[OH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH:13]1[CH2:14][CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:10])[CH2:12]1

Participants

3

Reactant 1

HCID 448908311-((Phenylmethoxy)carbonyl)-3-piperidinebutanoic acid

Product 1

HCID 58306139Phenylmethyl 3-(4-hydroxybutyl)-1-piperidinecarboxylateYield 95.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-(1-{[(phenylmethyl)oxy]carbonyl}-3-piperidinyl)butanoic acid (5.01 g, 16.41 mmol) in dry THF (40 ml) at 0° C. under nitrogen was added a solution of Borane-THF complex, (1M soln. in THF) (49.2 ml, 49.2 mmol), dropwise over 1 hour. The mixture was allowed to stir at 0° C. and gradually allowed to warm to rt over 20 hours. The mixture was cooled in an ice bath and cautiously quenched with dropwise addition of MeOH (20 ml) stirred in the cold bath for 2 hours then quenched further with 10% 2N HCl/MeOH (20 ml), stirred for 1 hour at rt and evaporated under reduced pressure. The residue was co-evaporated with methanol several times. The sample was purified by chromatography on silica (100 g, loaded in dichloromethane/EtOAc) using a gradient of 0-100% ethyl acetate in cyclohexane over 30 mins. collecting all 45 ml fractions on the Flashmaster II. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a colourless oil (4.55 g).

Workup

  1. temperatureto warm to rt over 20 hours
  2. temperatureThe mixture was cooled in an ice bath
  3. customcautiously quenched with dropwise addition of MeOH (20 ml)
  4. stirringstirred in the cold bath for 2 hours
  5. customthen quenched further with 10% 2N HCl/MeOH (20 ml)
  6. stirringstirred for 1 hour at rt
  7. customevaporated under reduced pressure
  8. customThe sample was purified by chromatography on silica (100 g, loaded in dichloromethane/EtOAc)
  9. customover 30 mins
  10. customcollecting all 45 ml fractions on the Flashmaster II
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-1ab6b19f0e1e4bec9b051395524b2337
Source dataset
uspto-grants-2013_10
Patent number
US08563717B2

Reaction notes

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