Methanol → 1-N-Boc-4-Piperidinecarboxylic acid methyl ester

HRID 1901079Notes

Reaction equation

HRID 1901079 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:16][CH2:15][CH:11]([C:12]([OH:14])=[O:13])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.[CH3:19][Si](C=[N+]=[N-])(C)C>C1C=CC=CC=1>[CH3:19][O:13][C:12](=[O:14])[CH:11]1[CH2:15][CH2:16][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]1

Participants

5

Reactant 3

HCID 887MethanolHCID 167693TrimethylsilyldiazomethaneHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid

Product 1

HCID 3928701-N-Boc-4-Piperidinecarboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To an ice cold solution of N-t-butoxycarbonyl isonipecotic acid (8.8 g, 34.9 mmol), in a 10% mixture of methanol in benzene (250 ml), was added a 2.0 M solution of trimethylsilyldiazomethane in hexanes, dropwise, until a consistent yellow color was obtained (~30 ml). After vigorous gas evolution had ceased, cooling was removed and the reaction mixture stirred for 1 h at room temperature. The mixture was then treated dropwise with glacial acetic acid until all yellow color had dissipated. It was then stirred 15 min. and concentrated in vacuo to a pale yellow oil. This material was purified by column chromatography on silica with 20% EtOAc/hexane as eluent. The appropriate fractions were combined and concentrated in vacuo to afford the product as a colorless oil.

Workup

  1. customdropwise, until a consistent yellow color was obtained (~30 ml)
  2. temperaturecooling
  3. customwas removed
  4. additionThe mixture was then treated dropwise with glacial acetic acid until all yellow color
  5. stirringIt was then stirred 15 min.
  6. concentrationconcentrated in vacuo to a pale yellow oil
  7. customThis material was purified by column chromatography on silica with 20% EtOAc/hexane as eluent
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7578914120cf4334ac18046f5aed4093
Source dataset
uspto-grants-1996_11
Patent number
US05576313

Reaction notes

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