O-Phenylenediamine → N1-(1-benzylpiperidin-4-yl)benzene-1,2-diamine

HRID 1068152Notes

Reaction equation

HRID 1068152 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]1([NH2:22])[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH2:21].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:21][C:16]2[C:15]([NH2:22])=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7243O-PhenylenediamineHCID 192201-Benzyl-4-piperidoneHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 93779N1-(1-benzylpiperidin-4-yl)benzene-1,2-diamineYield 44.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1.0 g 1-benzyl4-piperidone and 1.14 g of 1,2-phenylenediamine in 15 mL of THF was added two spatula tips of molecular sieves 4Å. After stirring at room temperature for 10 minutes, 1.34 g of sodium triacetoxyborohydride was added and the reaction was stirred at room temperature for 18 hours. The reaction was quenched with 50 mL of CH3OH and diluted with EtOAc. After filtering molecular sieves, the filtrate was concentrated under reduced pressure. The residue was partitioned between 50 mL of EtOAc and 30 ml saturated NaHCO3 aqueous solution. After separating layers, the aqueous phase was extracted with 2×50 mL EtOAc. The combined organic phases were washed with 15 mL of brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with 100% EtOAc, then 90% EtOAc in CH3OH to give 666 mg of the title compound as a solid. 1H NMR (400 MHz, CDCl3): δ1.56 (m, 2H), 2.07 (m, 2H), 2.18(m, 2H), 2.87 (d, J=11.6 Hz, 2H), 3.29(m, 1H), 3.56(s, 2H), 6.69 (m, 3H), 6.72(m, 1H), 7.25-7.61(m, 5H). ESI-MS 282 (M+H); HPLC A: 1.92 min.

Workup

  1. stirringthe reaction was stirred at room temperature for 18 hours
  2. customThe reaction was quenched with 50 mL of CH3OH
  3. additiondiluted with EtOAc
  4. filtrationAfter filtering molecular sieves
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was partitioned between 50 mL of EtOAc and 30 ml saturated NaHCO3 aqueous solution
  7. customAfter separating layers
  8. extractionthe aqueous phase was extracted with 2×50 mL EtOAc
  9. washThe combined organic phases were washed with 15 mL of brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by flash chromatography
  13. washeluting with 100% EtOAc

Sources & evidence

ORD record
ord-a04d539bc1634267ba0ab3ad44f7e14f
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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