Ammonia → HCID 89442531, compound

HRID 632722Notes

Reaction equation

HRID 632722 reaction equation
[C:1]([CH:3]([C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=1)[CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)#[N:2].N>CO.[OH-].[OH-].[Pd+2].[Ni]>[NH2:2][CH2:1][CH:3]([CH:4]1[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][CH2:9]1)[C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:24])[F:25])=[CH:19][CH:18]=1

Participants

6

Reactant 2

HCID 222AmmoniaHCID 68968606HCID 68968606, compound

Product 1

HCID 89442531HCID 89442531, compound

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent2×

Procedure

A solution of Intermediate (51.1) (2000.0 mg; 5.46 mmol; 1.00 eq.) in 50 ml of methanol was surged on H-Qube through 20% Pd(OH)2 cartridge at 1.5 ml/min and RT for one cycle. LCMS showed a clean product as tert-butyl 4-(cyano(4-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxylate. 10 ml of 7.0N NH3 in methanol was added to the above solution and the solution was then placed on H-Qube through Raney Ni column as cartridge at 1.5 ml/min and 45° C. for one cycle. LCMS showed clean reaction of reducing nitrile. The reaction mixture was concentrated to afford tert-butyl 4-(2-amino-1-(4-(trifluoromethyl)phenyl)ethyl)-piperidine-1-carboxylate, which was added 10 ml of 4.0M HCl in dioxane and stirred at RT for 4 hr. The precipitate was collected by filtration to yield the title compound as white solid (1600 mg, yield 77.7%). LC-MS: (M+1=273, obsd.=273).

Workup

  1. concentrationThe reaction mixture was concentrated

Sources & evidence

ORD record
ord-fd53902ea2cf4e5cbdb77bd0050fa2f6
Source dataset
uspto-grants-2016_04
Patent number
US09321760B2

Reaction notes

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