Cesium carbonate → Tert-butyl4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperidine-1-carboxylate

HRID 2383361Notes

Reaction equation

HRID 2383361 reaction equation
[CH:1]1([C@@:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([C:9]2[N:13]=[CH:12][NH:11][N:10]=2)[OH:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[C:31]([O:30][C:28]([N:25]1[CH2:26][CH2:27][CH:22]([CH2:21][N:11]2[CH:12]=[N:13][C:9]([C@:7]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)([OH:8])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:10]2)[CH2:23][CH2:24]1)=[O:29])([CH3:34])([CH3:32])[CH3:33]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 178519502HCID 178519502, compound

Product 1

HCID 59145956Tert-butyl4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperidine-1-carboxylateYield 64%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
70 °C

Procedure

(R)-cyclohexyl(phenyl)1H-1,2,4-triazol-3-ylmethanol (Preparation 2, 3.0 g, 11.7 mmol) was dissolved in acetone (60 mL) and tert-butyl 4-(bromomethyl)piperidine-1-carboxylate (3.24 g, 11.7 mmol) added, followed by cesium carbonate (7.60 g, 23.3 mmol). After stirring at 70° C. for 5 hours, the reaction was allowed to cool to room temperature and stirred for a further 16 hours. The solvent was removed in vacuo, and the residue partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was separated, dried over magnesium sulphate, filtered and the solvent removed in vacuo. 100 mg of this residue was dissolved in acetonitrile (0.5 ml) and left to evaporate, almost to dryness, at which point the resulting oil began to crystallise. The remainder of the residue was dissolved in acetonitrile (55 ml) and seeded with the crystalline material obtained above. Crystallisation was allowed to occur over 18 hours and the resulting solid collected by filtration to furnish the title compound as a white solid, in 64% yield, 3.4 g.

Workup

  1. temperatureto cool to room temperature
  2. stirringstirred for a further 16 hours
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between ethyl acetate (50 mL) and water (50 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. dissolution100 mg of this residue was dissolved in acetonitrile (0.5 ml)
  10. waitleft
  11. customto evaporate, almost to dryness, at which point the resulting oil
  12. customto crystallise
  13. dissolutionThe remainder of the residue was dissolved in acetonitrile (55 ml)
  14. customobtained above
  15. customCrystallisation
  16. waitto occur over 18 hours
  17. filtrationthe resulting solid collected by filtration

Sources & evidence

ORD record
ord-d8e2ed02ec4d4849a657b5a6613f81d0
Source dataset
uspto-grants-2012_09
Patent number
US08263623B2

Reaction notes

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