Sodium Methoxide → tert-butyl (3RS,4RS)-4-(5-benzyloxy-pyrimidin-2-yl)-3-hydroxy-piperidine-1-carboxylate

HRID 1858832Notes

Reaction equation

HRID 1858832 reaction equation
C(O)(=O)C.[C:5]([CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]1[OH:21])(=[NH:7])[NH2:6].C[O-].[Na+].[CH2:25]([O:32][C:33](=[CH:36]N(C)C)[CH:34]=O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CO>[CH2:25]([O:32][C:33]1[CH:34]=[N:7][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:10][CH:9]2[OH:21])=[N:6][CH:36]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 545210022-Benzyloxy-3-(dimethylamino)acroleinHCID 86604511tert-butyl (3RS,4RS)-4-carbamimidoyl-3-hydroxy-piperidine-1-carboxylate acetate

Product 1

HCID 54513866tert-butyl (3RS,4RS)-4-(5-benzyloxy-pyrimidin-2-yl)-3-hydroxy-piperidine-1-carboxylateYield 27.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 372 mg (1 mmol) of tert-butyl (3RS,4RS)-4-carbamimidoyl-3-hydroxy-piperidine-1-carboxylate acetate in 10 ml of methanol was treated with 1 ml of 1N sodium methylate solution and stirred at room temperature. Subsequently,205 mg (1 mmol) of 2-benzyloxy-3-dimethylamino-acrolein (EPA 0 477 901) were added thereto and the solution was heated to reflux for 18 hours. For the working-up, the reaction mixture was evaporated under reduced pressure and the residue was taken up in 20 ml of methylene chloride and washed with 5 ml of water. The organic phase was separated, dried over sodium sulphate and finally evaporated under reduced pressure. For purification, the residue was chromatographed on silica gel using a 1:4 mixture of methylene chloride and ethyl acetate as the eluent. There were obtained 106 mg (27% of theory) of tert-butyl (3RS,4RS)-4-(5-benzyloxy-pyrimidin-2-yl)-3-hydroxy-piperidine-1-carboxylate as a colourless oil; MS: 386 (M+H)+.

Workup

  1. temperaturethe solution was heated
  2. temperatureto reflux for 18 hours
  3. customthe reaction mixture was evaporated under reduced pressure
  4. washwashed with 5 ml of water
  5. customThe organic phase was separated
  6. dry with materialdried over sodium sulphate
  7. customfinally evaporated under reduced pressure
  8. customFor purification
  9. customthe residue was chromatographed on silica gel using
  10. additiona 1:4 mixture of methylene chloride and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-ee383aa54a2b453d821beac23f1bffe5
Source dataset
uspto-grants-2000_11
Patent number
US06150526

Reaction notes

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