Ethyl diazoacetate → Ethyl 1-benzyloxycarbonylpiperidine-4-oxyacetate

HRID 1900911Notes

Reaction equation

HRID 1900911 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([OH:17])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+](=[CH:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[N-]>ClCCl.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Rh+3].[Rh+3]>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([O:17][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 12192Ethyl diazoacetateHCID 2794620Benzyl 4-Hydroxy-1-piperidinecarboxylate

Product 1

HCID 23370004Ethyl 1-benzyloxycarbonylpiperidine-4-oxyacetate

Reagents, catalysts & solvents 2

HCID 86657289Di-rhodium tetraacetateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of N-benzyloxycarbonyl-4-hydroxypiperidine (2.4 g, preparation described by Alig, L. et al (1992), J. Med. Chem. 35, 4393), dirhodium tetraacetate (40 mg) and dichloromethane (15 ml) under argon was added dropwise over 3-4 hours, with stirring, a solution of ethyl diazoacetate (1.2 ml) in dichloromethane (2.5 ml). On completion of the addition, the reaction mixture was stirred at ambient temperature overnight and then evaporated. The resultant oily residue was purified by column chromatography on silica eluting with 30% ethyl acetate/hexane to give ethyl N-(benzyloxycarbonyl)piperidin-4-yloxyacetate (2.4 g) as a colourless oil: NMR Spectrum (CDCl3) 1.20 (3H, t), 1.40 (2H, m), 1.82 (2H, m), 3.13 (2H, m), 3.57 (1H, m), 3.70 (2H, m), 4.11 (2H, q), 4.13 (2H, s), 5.07 (2H, s), 7.35 (5H, m); Mass Spectrum m/Z 322 (M+H)+.

Workup

  1. additionwas added dropwise over 3-4 hours
  2. additionOn completion of the addition
  3. stirringthe reaction mixture was stirred at ambient temperature overnight
  4. customevaporated
  5. customThe resultant oily residue was purified by column chromatography on silica eluting with 30% ethyl acetate/hexane

Sources & evidence

ORD record
ord-d958b9f3d7ee44959f667ba7c35411ec
Source dataset
uspto-grants-1996_11
Patent number
US05576334

Reaction notes

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