Methanol → 2-(Methyloxy)-4-(4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}-1-piperidinyl)aniline

HRID 419370Notes

Reaction equation

HRID 419370 reaction equation
[BH4-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([N:14]2[CH2:19][CH2:18][CH:17]([N:20]3[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH2:22][CH2:21]3)[CH2:16][CH2:15]2)[CH:8]=[CH:9][C:10]=1[N+:11]([O-])=O.CO>O.O.O.O.O.O.[Ni](Cl)Cl.C1COCC1>[CH3:3][O:4][C:5]1[CH:6]=[C:7]([N:14]2[CH2:15][CH2:16][CH:17]([N:20]3[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][S:28]([CH3:31])(=[O:29])=[O:30])[CH2:24][CH2:25]3)[CH2:18][CH2:19]2)[CH:8]=[CH:9][C:10]=1[NH2:11]

Participants

6

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 598602741-{1-[3-(Methyloxy)-4-nitrophenyl]-4-piperidinyl}-4-[2-(methylsulfonyl)ethyl]piperazine

Product 1

HCID 598602832-(Methyloxy)-4-(4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}-1-piperidinyl)anilineYield 68%

Reagents, catalysts & solvents 2

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

NaBH4 (2.64 g, 69.8 mmol) was added carefully in portions to a suspension of 1-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-4-[2-(methylsulfonyl)-ethyl]piperazine (9.9 g, 23.3 mmol), nickel(II)chloride hexahydrate (1.66 g, 7 mmol), MeOH (120 mL) and THF (60 mL) at 0° C. The ice bath was removed and the reaction mixture was stirred at rt overnight (˜16 h). The reaction mixture was concentrated onto silica gel and flash chromatography afforded the title compound of step B (6.24 g, 68%) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ 6.49-6.44 (m, 2H), 6.26 (dd, J=8.4, 2.6 Hz, 1H), 4.18 (bs, 2H), 3.71 (s, 3H), 3.43-3.36 (m, 2H), 3.25 (t, J=6.8 Hz, 2H), 3.00 (s, 3H), 2.65 (t, J=6.8 Hz, 2H), 2.47-2.36 (m, 4H), 2.23-2.15 (m, 1H), 1.82-1.75 (m, 2H), 1.54-1.43 (m, 2H).

Workup

  1. customThe ice bath was removed
  2. concentrationThe reaction mixture was concentrated onto silica gel and flash chromatography

Sources & evidence

ORD record
ord-31a164ef948b40978436aa5d7e67d0e6
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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