Acetic Anhydride → Tert-butyl 4-acetoxypiperidine-1-carboxylate

HRID 518814Notes

Reaction equation

HRID 518814 reaction equation
[C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].OC1C[CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1>N1C=CC=CC=1>[C:5]([O:4][CH:1]1[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:13][CH2:2]1)(=[O:7])[CH3:6]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 21660336Tert-butyl 4-acetoxypiperidine-1-carboxylateYield 62%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

4.75 g of di-tert-butyl dicarbonate are added to a mixture of 2 g of 4-hydroxypiperidine in 4 ml of water and 13.8 ml of a 2N aqueous sodium hydroxide solution. The reaction medium is stirred at ambient temperature for 2 hours and then 50 ml of chloroform are added. The two phases are separated and the organic phase is washed with an aqueous 25% NH4OH solution and then with a saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulfate, filtered and evaporated, so as to give 4 g of 2-methylpropan-2-yl 4-hydroxypiperidine-1-carboxylate in the form of a colourless oil. 2.84 g of acetic anhydride are added to a solution of 4.0 g of 2-methylpropan-2-yl 4-hydroxypiperidine-1-carboxylate in 6 ml of pyridine. The reaction medium is stirred for hours at ambient temperature and then concentrated to dryness. The residue is taken up in dichloromethane and an aqueous 25% NH4OH solution. The two phases are separated and the organic phase is washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and evaporated. Purification is carried out by flash chromatography on silica gel (40-63 μm), elution being carried out with a mixture of dichloromethane and MeOH (95/5), so as to obtain 3 g of 2-methylpropan-2-yl 4-(acetyloxy)piperidine-1-carboxylate in the form of a colourless oil.

Workup

  1. concentrationconcentrated to dryness
  2. customThe two phases are separated
  3. washthe organic phase is washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification
  8. washis carried out by flash chromatography on silica gel (40-63 μm), elution
  9. additionbeing carried out with a mixture of dichloromethane and MeOH (95/5)

Sources & evidence

ORD record
ord-e244ee2587ed41499f6957d5d82ecc55
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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