N-(4-chlorophenyl)piperidin-4-amine → (2R,3R)-3-(4-(4-chlorophenylamino)piperidin-1-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol

HRID 1430084Notes

Reaction equation

HRID 1430084 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.Cl([O-])(=O)(=O)=O.[Li+].[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[C@@:29]1([CH2:33][N:34]2[CH:38]=[N:37][CH:36]=[N:35]2)[C@@H:31]([CH3:32])[O:30]1>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C@H:31]([CH3:32])[C@:29]([C:23]3[CH:24]=[CH:25][C:26]([F:28])=[CH:27][C:22]=3[F:21])([OH:30])[CH2:33][N:34]3[CH:38]=[N:37][CH:36]=[N:35]3)[CH2:11][CH2:10]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7183033N-(4-chlorophenyl)piperidin-4-amineHCID 107058781-(((2R,3R)-2-(2,4-difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazoleHCID 23665649Lithium perchlorate

Product 1

HCID 67369730(2R,3R)-3-(4-(4-chlorophenylamino)piperidin-1-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-olYield 31%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of the N-(4-chlorophenyl)piperidine-4-amine (400.0 mg, 1.9 mmol) obtained in step 2 in acetonitrile were added lithium perchlorate (134.1 mg, 1.3 mmol) and 1-(((2R,3R)-2-(2,4-difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole (158.9 mg, 0.6 mmol), followed by irradiating microwaves onto the solution at 150° C. for 30 min. After removal of the solvent, the reaction mixture was diluted in ethyl acetate and washed with distilled water and saline to separate an organic solvent layer. The organic solvent layer was dried over anhydrous magnesium sulfate and concentrated in a vacuum. Isolation and purification of the concentrate through silica gel chromatography afforded the title compound (yield 31%).

Workup

  1. customby irradiating microwaves onto the solution at 150° C. for 30 min
  2. customAfter removal of the solvent
  3. additionthe reaction mixture was diluted in ethyl acetate
  4. washwashed with distilled water and saline
  5. customto separate an organic solvent layer
  6. dry with materialThe organic solvent layer was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated in a vacuum
  8. customIsolation and purification of the
  9. concentrationconcentrate through silica gel chromatography

Sources & evidence

ORD record
ord-7e9cea6bcd6e4b68a21376436ab053bb
Source dataset
uspto-grants-2015_01
Patent number
US08940768B2

Reaction notes

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