tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 11998644, compound

HRID 1159009Notes

Reaction equation

HRID 1159009 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C@H:11]([CH3:28])[C@:12]([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[F:27])([OH:19])[CH2:13][N:14]1[CH:18]=[N:17][CH:16]=[N:15]1)[N:6]=[CH:5]2.O=[C:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]1.C([BH3-])#N.[Na+]>C(O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[C@@:12]([OH:19])([CH2:13][N:14]1[CH:18]=[N:17][CH:16]=[N:15]1)[C@H:11]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([NH:1][CH:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)=[CH:10][CH:9]=2)[CH:5]=[N:6]1)[CH3:28]

Participants

6

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydrideHCID 16729634HCID 16729634, compound

Product 1

HCID 11998644HCID 11998644, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

To a solution of (2R,3R)-3-(5-amino-1H-indazol-1-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (0.419 g, 1.09 mmol) and tert-butyl 4-oxo-1-piperidine carboxylate (0.22 g, 1.09 mmol) in absolute ethanol (2 ml) was added titanium (IV) isopropoxide (0.358 ml, 1.20 mmol), and the solution was stirred at room temperature for 2 hours. The addition of sodium cyanotrihydridoborate (0.137 g, 2.18 mmol) to the solution was followed by stirring at room temperature for 18 hours. The reaction was terminated by adding 10% sodium hydroxide solution (2 ml) before extraction with dichloromethane (20 ml). The organic layer was dried over anhydrous magnesium sulfate and evaporated in a vacuum to concentrate it. The crude product was purified by chromatography on silica gel to give the title compound (Yield 52%).

Workup

  1. stirringby stirring at room temperature for 18 hours
  2. customThe reaction was terminated
  3. additionby adding 10% sodium hydroxide solution (2 ml)
  4. extractionbefore extraction with dichloromethane (20 ml)
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. customevaporated in a vacuum
  7. concentrationto concentrate it
  8. customThe crude product was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-789110f8bfcf4a28823d9d6b9c07dfe0
Source dataset
uspto-grants-2010_10
Patent number
US07812045B2

Reaction notes

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