Sodium borohydride → 2-Methoxy-4-[4-(1-piperidyl)-1-piperidyl]aniline

HRID 419330Notes

Reaction equation

HRID 419330 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-])=O.[BH4-].[Na+]>CO.C1COCC1.O.O.O.O.O.O.[Ni](Cl)Cl>[N:18]1([CH:15]2[CH2:16][CH2:17][N:12]([C:5]3[CH:6]=[CH:7][C:8]([NH2:9])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:13][CH2:14]2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

6

Reactant 2

HCID 4311764Sodium borohydride2×HCID 587483781'-[3-(Methyloxy)-4-nitrophenyl]-1,4'-bipiperidine

Product 1

HCID 597120872-Methoxy-4-[4-(1-piperidyl)-1-piperidyl]anilineYield 89%

Reagents, catalysts & solvents 3

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 1′-[3-(methyloxy)-4-nitrophenyl]-1,4′-bipiperidine (47.9 g, 150 mmol) and nickel(II) chloride hexahydrate (17.8 g, 75.0 mmol) in MeOH (600 mL) and THF (300 mL) cooled to 0° C. was added NaBH4 (˜30 g, ˜750 mmol) at such a rate to control the foaming which occurred. NaBH4 was added until the yellow color disappeared from the foam (TLC confirms consumption of starting material). The mixture was rotovaped down and placed on the high vacuum overnight. EtOAc (1000 mL) was added to the solid and the slurry was stirred for 3 h. The mixture was filtered through a pad of celite, rinsing with generous amounts of EtOAc. The filtrate was washed with 0.1N NaOH (2×1000 mL), dried (MgSO4), filtered, and rotovaped down to give the title compound (38.3 g, 133 mmol, 89%) as a pink solid. 1H NMR (400 MHz, CDCl3) δ 6.60 (d, J=8.4 Hz, 1H), 6.49 (d, J=2.4 Hz, 1H), 6.38 (dd, J=8.4, 2.4 Hz, 1H), 3.80 (s, 3H), 3.52-3.45 (m, 4H), 2.61-2.47 (m, 6H), 2.36-2.27 (m, 1H), 1.90-1.63 (m, 4H), 1.61-1.52 (m, 4H), 1.45-1.36 (m, 2H).

Workup

  1. customdisappeared from the foam (TLC confirms consumption of starting material)
  2. customplaced on the high vacuum overnight
  3. additionEtOAc (1000 mL) was added to the solid
  4. filtrationThe mixture was filtered through a pad of celite
  5. washrinsing with generous amounts of EtOAc
  6. washThe filtrate was washed with 0.1N NaOH (2×1000 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered

Sources & evidence

ORD record
ord-de37598323ea4db4b17db8b1d718a00c
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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