Methyl iodide → Ethyl trans-4-azido-3-methoxy-1-piperidinecarboxylate

HRID 981297Notes

Reaction equation

HRID 981297 reaction equation
[K].[N:2]([C@@H:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][C@H:6]1[OH:16])=[N+:3]=[N-:4].N([C@H:20]1[C@H](O)CCN(C(OCC)=O)C1)=[N+]=[N-].IC>O.CN(C)C=O.CC(O)(C)C>[N:2]([C@@H:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][C@H:6]1[O:16][CH3:20])=[N+:3]=[N-:4]

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 5462222PotassiumHCID 13677846Ethyl trans-4-azido-3-hydroxy-1-piperidinecarboxylateHCID 86744575Ethyl trans-3-azido-4-hydroxy-1-piperidinecarboxylate

Product 1

HCID 13677848Ethyl trans-4-azido-3-methoxy-1-piperidinecarboxylateYield 48.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6386tert-ButanolSolvent

Procedure

To a stirred solution of 20.6 parts of 2-methyl-2-propanol, potassium salt in 54 parts of N,N-dimethylformamide was added dropwise a solution of 30.3 parts of a mixture of ethyl trans-4-azido-3-hydroxy-1-piperidinecarboxylate and ethyl trans-3-azido-4-hydroxy-1-piperidinecarboxylate in 45 parts of N,N-dimethylformamide at a temperature below 20° C. (ice bath). Upon completion, stirring was continued for 1 hour at room temperature. 25.9 parts of iodomethane were added dropwise at a temperature <10° C. Upon completion, stirring was continued overnight at room temperature. The reaction mixture was poured into 400 parts of water. The product was extracted with trichloromethane. The extract was washed with a sodium chloride solution, dried, filtered and evaporated in vacuo. The residue was purified by column chromatography over silica gel using trichloromethane as eluent. The desired fractions were collected and the eluent was evaporated, yielding 15.6 parts (48.8%) of ethyl trans-4-azido-3-methoxy-1-piperidinecarboxylate as a residue (interm. 4).

Workup

  1. stirringUpon completion, stirring
  2. waitwas continued overnight at room temperature
  3. extractionThe product was extracted with trichloromethane
  4. washThe extract was washed with a sodium chloride solution
  5. customdried
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by column chromatography over silica gel
  9. customThe desired fractions were collected
  10. customthe eluent was evaporated

Sources & evidence

ORD record
ord-b4db6458363a439d9801b1fcedc5020f
Source dataset
uspto-grants-1991_02
Patent number
US04990521

Reaction notes

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