Benzylamine → Ethyl trans-3-hydroxy-4-[(phenylmethyl)amino]-1-piperidinecarboxylate

HRID 345539Notes

Reaction equation

HRID 345539 reaction equation
[CH:1]12[O:7][CH:6]1[CH2:5][CH2:4][N:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:2]2.[C:13]1([CH2:19][NH2:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(O)C>[OH:7][C@H:1]1[C@H:6]([NH:20][CH2:19][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:5][CH2:4][N:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:2]1.[OH:7][C@@H:6]1[CH2:5][CH2:4][N:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:2][C@H:1]1[NH:20][CH2:19][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 2

HCID 7504BenzylamineHCID 12414163Ethyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate2×

Product 2

HCID 13677850Ethyl trans-3-hydroxy-4-[(phenylmethyl)amino]-1-piperidinecarboxylateHCID 67312643Ethyl trans-4-hydroxy-3-[(phenylmethyl)amino]-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 3.4 parts of ethyl 7-oxa-3-azabicyclo[4,1,0]heptane-3-carboxylate, 2.1 parts of benzenemethanamine and 40 parts of ethanol was stirred and refluxed for 17 hours. Another 0.3 parts of ethyl 7-oxa-3-azabicyclo[4,1,0]heptane-3-carboxylate were added and stirring at reflux was continued for 4 hours. The reaction mixture was evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (97:3 by volume) as eluent. The pure fractions were collected and the eluent was evaporated, yielding 3.4 parts (61.8%) of a mixture of ethyl trans-3-hydroxy-4-[(phenylmethyl)amino]-1-piperidinecarboxylate and ethyl trans-4-hydroxy-3-[(phenylmethyl)amino]-1-piperidinecarboxylate as an oily residue (intermediate 35 and 36).

Workup

  1. temperaturerefluxed for 17 hours
  2. stirringstirring
  3. temperatureat reflux
  4. customThe reaction mixture was evaporated
  5. customThe residue was purified by column-chromatography over silica gel using
  6. additiona mixture of trichloromethane and methanol (97:3 by volume) as eluent
  7. customThe pure fractions were collected
  8. customthe eluent was evaporated

Sources & evidence

ORD record
ord-7e65da6c0a2e4c6e8112a9f63e6911ff
Source dataset
uspto-grants-1991_10
Patent number
US05057525

Reaction notes

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