Methyl iodide → Tert-butyl 4-cyclohexyl-4-methoxy-1-piperidinecarboxylate

HRID 1816358Notes

Reaction equation

HRID 1816358 reaction equation
[CH:1]1([C:7]2([OH:20])[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:23]I>CN(C=O)C>[CH:1]1([C:7]2([O:20][CH3:23])[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:9][CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 22492872Tert-butyl 4-cyclohexyl-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 22492894Tert-butyl 4-cyclohexyl-4-methoxy-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 4-cyclohexyl-4-hydroxy-1-piperidinecarboxylate (7.26 g) in DMF (70 ml) was added sodium hydride (60% in oil) (2.05 g) with stirring under ice-cooling. The mixture was stirred at ambient temperature for 1 hour. To the suspension was added methyl iodide (4.79 ml) and the mixture was stirred at ambient temperature overnight. The reaction mixture was poured into ice-water (300 ml) and extracted three times with ethyl acetate (200 ml). The extracts were collected, washed twice with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated in vacuo. The resulting residue was chromatographed on silica gel (400 ml) eluting with a mixture of n-hexane and ethyl acetate (4:1 v/v). The fractions containing the desired compound were collected and evaporated under reduced pressure to give tert-butyl 4-cyclohexyl-4-methoxy-1-piperidinecarboxylate (6.77 g).

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred at ambient temperature for 1 hour
  3. stirringthe mixture was stirred at ambient temperature overnight
  4. extractionextracted three times with ethyl acetate (200 ml)
  5. customThe extracts were collected
  6. washwashed twice with saturated aqueous sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. customevaporated in vacuo
  9. customThe resulting residue was chromatographed on silica gel (400 ml)
  10. washeluting with a mixture of n-hexane and ethyl acetate (4:1 v/v)
  11. additionThe fractions containing the desired compound
  12. customwere collected
  13. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-1a48c849a52449c2acdc3931cf01c0b7
Source dataset
uspto-grants-2005_04
Patent number
US06884774B2

Reaction notes

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