Acetic Acid → 1-N-Boc-4-Piperidinecarboxylic acid methyl ester

HRID 443218Notes

Reaction equation

HRID 443218 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.C(O)(=O)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

6

Reactant 4

HCID 176Acetic AcidHCID 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 2.0M solution of trimethylsilyldiazomethane in hexanes, dropwise, until a consistent yellow color was obtained (~30 ml). After vigorous gas evolution had ceased, the reaction mixture was stirred for 1 hr at room temperature. The mixture was then treated dropwise with glacial acetic acid until the yellow color had dissipated. The reaction was stirred 15 min. and concentrated in vacuo to a pale yellow oil. The residue was purified by chromatography (SiO2, eluting with 20% EtOAc in hexanes). Evaporation of the solvent in vacuo afforded the product as a colorless oil.

Workup

  1. customdropwise, until a consistent yellow color was obtained (~30 ml)
  2. stirringThe reaction was stirred 15 min.
  3. concentrationconcentrated in vacuo to a pale yellow oil
  4. customThe residue was purified by chromatography (SiO2, eluting with 20% EtOAc in hexanes)
  5. customEvaporation of the solvent in vacuo

Sources & evidence

ORD record
ord-9328c7743fd74e9c86784601128762cd
Source dataset
uspto-grants-1999_04
Patent number
US05891889

Reaction notes

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