Ammonium Hydroxide → 4-[(Benzyl-methyl-amino)-methyl]-2-methoxy-phenylamine

HRID 1830784Notes

Reaction equation

HRID 1830784 reaction equation
[BH4-].[Na+].[CH2:3]([N:10]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[C:15]([O:22][CH3:23])[CH:14]=1)[CH3:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH4+].[OH-]>CCO.C1COCC1.B#[Ni].O.O.O.O.O.O.[Ni](Cl)Cl>[CH2:3]([N:10]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([NH2:19])=[C:15]([O:22][CH3:23])[CH:14]=1)[CH3:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 3

HCID 14923Ammonium HydroxideHCID 4311764Sodium borohydride2×HCID 22046408N-benzyl-(3-methoxy-4-nitro-benzyl)-methyl-amine

Product 1

HCID 220463124-[(Benzyl-methyl-amino)-methyl]-2-methoxy-phenylamineYield 65%

Reagents, catalysts & solvents 4

HCID 82791nickel boride (NiB)CatalystHCID 11791229Dichloronickel;hexahydrateCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Nickel boride Reduction General Method: To a stirred solution of nickel chloride hexahydrate (820 mg, 3.45 mmol) in 12 mL EtOH and 3 mL THF, at 0° C., NaBH4 (130 mg, 3.45 mmol) was added. The resulting black suspension was stirred at 0° C. while N-benzyl-(3-methoxy-4-nitro-benzyl)-methyl-amine was added as a solution in 5 mL THF. After several minutes, 260 mg of NaBH4 was added in several portions over 10 minutes, and the reaction mixture was subsequently allowed to warm to room temperature. After 2 h, TLC indicated complete conversion to a new, more polar product. At this point, 1.5 mL of 5% NH4OH was added and the reaction was stirred for about 10 min, until the black solids achieved a granular consistency. The reaction was filtered through a glass fiber filter, rinsing with THF. The clear colorless filtrate was concentrated to about ¼ volume, diluted with 30 mL water and extracted with EtOAc (3×30 mL). The combined extracts were washed with brine, dried over MgSO4 and filtered through a short plug of silica and concentrated in vacuo to afford 575 mg (65%) of the desired product as an off-white solid. 1H NMR (400 MHz, CDCl3): δ7.2-7.4 (m, 5H), 7.85 (s, 1H), 6.85 (s, 1H), 6.74 (d, J=8.2 Hz, 1H), 6.66 (d, J=8.2 Hz, 1H), 3.87 (s, 3H), 3.73 (br. s, 2H) 3.49 (s, 2H), 3.45 (s, 2H), 2.18 (s, 3H). MS (APCI-pos)M+1=256.9

Workup

  1. waitAfter several minutes
  2. filtrationThe reaction was filtered through a glass fiber
  3. filtrationfilter
  4. washrinsing with THF
  5. concentrationThe clear colorless filtrate was concentrated to about ¼ volume
  6. additiondiluted with 30 mL water
  7. extractionextracted with EtOAc (3×30 mL)
  8. washThe combined extracts were washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered through a short plug of silica
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-362df69026c140aa943c9afd2f72970c
Source dataset
uspto-grants-2006_06
Patent number
US07067506B2

Reaction notes

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