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

HRID 419367Notes

Reaction equation

HRID 419367 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]([S:26]([CH3:29])(=[O:28])=[O:27])[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[CH2:19][CH2:18][CH:17]([N:20]3[CH2:21][CH2:22][N:23]([S:26]([CH3:29])(=[O:28])=[O:27])[CH2:24][CH2:25]3)[CH2:16][CH2:15]2)[CH:8]=[CH:9][C:10]=1[NH2:11]

Participants

6

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 598602451-{1-[3-(Methyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine

Product 1

HCID 574161512-(Methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}anilineYield 90%

Reagents, catalysts & solvents 2

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

NaBH4 (1.18 g, 31.1 mmol) was added carefully in portions (exothermic) to a suspension of 1-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)-piperazine (3.54 g, 8.9 mmol), nickel(II)chloride hexahydrate (1.06 g, 4.4 mmol), MeOH (100 mL) and THF (50 mL) at 0° C. The ice bath was removed and the reaction mixture was warmed to rt. TLC analysis indicated the complete consumption of the starting material. The reaction mixture was concentrated onto silica gel and flash chromatography afforded the title compound of step B (2.93 g, 90%) as a colorless solid. 1H NMR (400 MHz, DMSO-d6) δ 6.49-6.46 (m, 2H), 6.27 (dd, J=8.5, 2.6 Hz, 1H), 4.18 (bs, 2H), 3.71 (s, 3H), 3.44-3.38 (m, 2H), 3.11-3.04 (m, 4H), 2.84 (s, 3H), 2.61-2.54 (m, 4H), 2.35-2.26 (m, 1H), 1.80-1.77 (m, 2H), 1.56-1.46 (m, 2H).

Workup

  1. customThe ice bath was removed
  2. customthe complete consumption of the starting material
  3. concentrationThe reaction mixture was concentrated onto silica gel and flash chromatography

Sources & evidence

ORD record
ord-f1c97651745d4972b79fd8d3daba0c10
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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