Methanol → 1-{4-[1-(4-Amino-3-methoxyphenyl)piperidin-4-yl]piperazin-1-yl}ethan-1-one

HRID 419373Notes

Reaction equation

HRID 419373 reaction equation
[BH4-].[Na+].[C:3]([N:6]1[CH2:11][CH2:10][N:9]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-])=O)=[C:20]([O:27][CH3:28])[CH:19]=3)[CH2:14][CH2:13]2)[CH2:8][CH2:7]1)(=[O:5])[CH3:4].CO>O.O.O.O.O.O.[Ni](Cl)Cl.C1COCC1>[C:3]([N:6]1[CH2:7][CH2:8][N:9]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([NH2:24])=[C:20]([O:27][CH3:28])[CH:19]=3)[CH2:14][CH2:13]2)[CH2:10][CH2:11]1)(=[O:5])[CH3:4]

Participants

6

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 574161491-Acetyl-4-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}piperazine

Product 1

HCID 574161481-{4-[1-(4-Amino-3-methoxyphenyl)piperidin-4-yl]piperazin-1-yl}ethan-1-oneYield 76%

Reagents, catalysts & solvents 2

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

NaBH4 (0.190 g, 5.06 mmol) was added carefully in portions (exothermic) to a suspension of 1-acetyl-4-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}piperazine (0.52 g, 1.45 mmol), nickel(II)chloride hexahydrate (0.170 g, 0.72 mmol), MeOH (8 mL) and THF (4 mL) at 0° C. The ice bath was removed and the reaction mixture was stirred at rt overnight (˜16 h). The solvent was evaporated and the residue was suspended in DCM and filtered through celite. Flash chromatography afforded the title compound of step B (0.36 g, 76%). 1H NMR (400 MHz, DMSO-d6) δ 6.50-6.45 (m, 2H), 6.30-6.25 (m, 1H), 4.18 (bs, 2H), 3.71 (s, 3H), 3.45-3.36 (m, 6H), 2.45-2.38 (m, 3H), 2.31-2.23 (m, 1H), 1.96 (s, 3H), 1.82-1.74 (m, 2H), 1.58-1.44 (m, 2H).

Workup

  1. customThe ice bath was removed
  2. customThe solvent was evaporated
  3. filtrationfiltered through celite

Sources & evidence

ORD record
ord-cd5c246465c94359802318ff68453711
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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