1-[3-(Ethyloxy)-4-nitrophenyl]-4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}-piperazine → [2-(Ethyloxy)-4-(4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}-1-piperazinyl)-phenyl]amine

HRID 419402Notes

Reaction equation

HRID 419402 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([N:13]2[CH2:18][CH2:17][N:16]([CH:19]3[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH2:21][CH2:20]3)[CH2:15][CH2:14]2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-])=O)[CH3:2]>CO.CCOC(C)=O.[Pt]>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([N:13]2[CH2:14][CH2:15][N:16]([CH:19]3[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][S:27]([CH3:30])(=[O:28])=[O:29])[CH2:21][CH2:20]3)[CH2:17][CH2:18]2)[CH:7]=[CH:8][C:9]=1[NH2:10])[CH3:2]

Participants

4

Reactant 1

HCID 666496531-[3-(Ethyloxy)-4-nitrophenyl]-4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}-piperazine

Product 1

HCID 66649831[2-(Ethyloxy)-4-(4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}-1-piperazinyl)-phenyl]amineYield 97%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 21584119Ethylacetate methanolSolvent

Procedure

A mixture of 1-[3-(ethyloxy)-4-nitrophenyl]-4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}-piperazine (290 mg, 0.65 mmol) and platinum (sulfided, 5 wt. % on carbon, 50 mg, 0.013 mmol) in 20% MeOH/EtOAc (20 mL) was added to a high-pressure hydrogenation reaction flask. The reaction was purged with N2 and vacuum (3×). The reaction was purged with H2 and vacuum (3×). The reaction was then treated with H2 at 50 psi and stirred for approximately 20 h. The reaction was degassed, then poured through a Teflon filter, washing the solid with MeOH and DCM. The filtrate was concentrated under vacuum to give the title compound of step B (256 mg, 0.62 mmol, 97%) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ 6.50 (d, 1H, J=8.43 Hz), 6.44 (d, 1H, J=2.38 Hz), 6.26 (cd, 1H, J=2.38 and 8.43 Hz), 4.17 (br s, 2H), 3.95 (q, 2H, J=6.96 Hz), 3.25 (t, 2H, J=6.69 Hz), 3.01 (s, 3H), 2.91 (M, 6H), 2.65 (t, 2H, J=6.78 Hz), 2.57 (m, 4H), 2.10-2.20 (m, 1H), 1.89-1.97 (m, 2H), 1.76 (m, 2H), 1.28-1.32 (m, 5H).

Workup

  1. additionwas added to a high-pressure hydrogenation reaction flask
  2. customThe reaction was purged with N2 and vacuum (3×)
  3. customThe reaction was purged with H2 and vacuum (3×)
  4. additionThe reaction was then treated with H2 at 50 psi
  5. customThe reaction was degassed
  6. additionpoured through a Teflon
  7. filtrationfilter
  8. washwashing the solid with MeOH and DCM
  9. concentrationThe filtrate was concentrated under vacuum

Sources & evidence

ORD record
ord-7491da6c900c43299fe29c57a2ee0dc1
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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