Sodium cyanoborohydride → (2R,3R)-2-(2,4-difluorophenyl)-3-((1-(2-fluorophenyl)piperidin-4-yl)amino)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol

HRID 1430086Notes

Reaction equation

HRID 1430086 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1.[NH2:15][C@H:16]([CH3:33])[C@:17]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=1[F:32])([OH:24])[CH2:18][N:19]1[CH:23]=[N:22][CH:21]=[N:20]1.C([BH3-])#N.[Na+]>C(O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:32][C:26]1[CH:27]=[C:28]([F:31])[CH:29]=[CH:30][C:25]=1[C@:17]([OH:24])([C@H:16]([NH:15][CH:11]1[CH2:12][CH2:13][N:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH2:9][CH2:10]1)[CH3:33])[CH2:18][N:19]1[CH:23]=[N:22][CH:21]=[N:20]1

Participants

6

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 10967497(2R,3R)-3-Amino-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-olHCID 111168931-(2-Fluorophenyl)piperidin-4-one

Product 1

HCID 53357279(2R,3R)-2-(2,4-difluorophenyl)-3-((1-(2-fluorophenyl)piperidin-4-yl)amino)-1-(1H-1,2,4-triazol-1-yl)butan-2-olYield 44%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

To a solution of 1-(2-fluorophenyl)piperidin-4-one (36.0 mg, 0.19 mmol) in anhydrous ethanol (1 mL) was added (2R,3R)-3-amino-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (50.0 mg, 0.19 mmol). While being stirred, the reaction solution was mixed at room temperature for four hrs with titanium (IV) isopropoxide (0.06 mL, 0.21 mmol) and then at room temperature for 18 hrs with sodium cyanoborohydride (35.0 mg, 0.56 mmol). The reaction was terminated by adding distilled water, after which the reaction mixture was concentrated by evaporation at reduced pressure and extracted with ethyl acetate to give an organic solvent layer. This organic layer was dried over anhydrous magnesium sulfate and purified by silica gel chromatography to afford the title compound (yield 44%).

Workup

  1. customThe reaction was terminated
  2. additionby adding
  3. distillationdistilled water
  4. concentrationafter which the reaction mixture was concentrated by evaporation at reduced pressure
  5. extractionextracted with ethyl acetate
  6. customto give an organic solvent layer
  7. dry with materialThis organic layer was dried over anhydrous magnesium sulfate
  8. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-ba8912afa48542edbf0779fbc4811086
Source dataset
uspto-grants-2015_01
Patent number
US08940768B2

Reaction notes

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