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

HRID 2383360Notes

Reaction equation

HRID 2383360 reaction equation
Br[CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[CH:16]1([C@@:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:24]2[N:28]=[CH:27][NH:26][N:25]=2)[OH:23])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:12]([O:11][C:9]([N:6]1[CH2:7][CH2:8][CH:3]([CH2:2][N:26]2[CH:27]=[N:28][C:24]([C@:22]([CH:29]3[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]3)([OH:23])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:25]2)[CH2:4][CH2:5]1)=[O:10])([CH3:15])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 11430Potassium 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 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Tert-butyl 4-(bromomethyl)piperidine-1-carboxylate (6.75 g, 24.2 mmol) was dissolved in DMF (62 ml) and (R)-cyclohexyl(phenyl)1H-1,2,4-triazol-3-ylmethanol (Preparation 2, 5.2 g, 20 mmol) added, followed by potassium carbonate (5.58 g, 40.4 mmol). After stirring at 70° C. for 18 hours the solvent was removed in vacuo, and the residue partitioned between ethyl acetate (150 ml) and water (150 mL). The organic layer was separated, dried over magnesium sulphate, filtered and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with ethyl acetate:heptane, (1:4 to 1:1, by volume) to furnish the title compound as a white foam, in 51% yield, 4.7 g (contains 10% of the other riazole regio-isomer).

Workup

  1. customwas removed in vacuo
  2. customthe residue partitioned between ethyl acetate (150 ml) and water (150 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customThe residue was purified by column chromatography on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-d078bd1511b84418998344ba5caae562
Source dataset
uspto-grants-2012_09
Patent number
US08263623B2

Reaction notes

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