(R)-3-[4-(4-methoxy-phenylamino)-piperidin-1-yl]-butyronitrile → (R)-[1-(3-amino-1-methyl-propyl)-piperidin-4-yl]-(4-methoxy-phenyl)-amine

HRID 1782584Notes

Reaction equation

HRID 1782584 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([C@H:16]([CH3:20])[CH2:17][C:18]#[N:19])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1>N.[Ni].CO>[NH2:19][CH2:18][CH2:17][C@H:16]([N:13]1[CH2:12][CH2:11][CH:10]([NH:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH2:15][CH2:14]1)[CH3:20]

Participants

5

Reactant 1

HCID 68969354(R)-3-[4-(4-methoxy-phenylamino)-piperidin-1-yl]-butyronitrile

Product 1

HCID 68970439(R)-[1-(3-amino-1-methyl-propyl)-piperidin-4-yl]-(4-methoxy-phenyl)-amine

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 222AmmoniaSolventHCID 887MethanolSolvent

Procedure

(R)-3-[4-(4-Methoxy-phenylamino)-piperidin-1-yl]-butyronitrile (0.53 g, 1.94 mmol) was dissolved in NH3 saturated MeOH (15 mL), treated with Raney nickel (excess), and placed under 45 psi H2 on a Parr shaker for 8 h. In a standard work-up the mixture was diluted with MeOH and filtered through celite. The cake was washed with MeOH and the combined filtrate was concentrated to give crude (R)-[1-(3-amino-1-methyl-propyl)-piperidin-4-yl]-(4-methoxy-phenyl)-amine as a pale yellow oil (0.54 g, quant.). TLC analysis and 1H NMR confirmed the crude product to be pure with no further purification required. 1H NMR (CDCl3) δ 0.98 (d, 3H, J=6.0 Hz), 1.36 (m, 5H), 1.71 (m, 2H), 2.03 (d, 2H, J=12.0 Hz), 2.23 (br t, 1H), 2.42 (br t, 1H), 2.49-2.71 (m, 4H), 3.17 (m, 2H), 3.76 (s, 3H), 6.57 (d, 2H, J=9.0 Hz), 6.75 (d, 2H, J=9.0 Hz).

Workup

  1. filtrationfiltered through celite
  2. washThe cake was washed with MeOH
  3. concentrationthe combined filtrate was concentrated

Sources & evidence

ORD record
ord-923f14f00a2b451ba7dd9e5e227f76e2
Source dataset
uspto-grants-2009_03
Patent number
US07498346B2

Reaction notes

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