1,2-Diaminocyclohexane, trans- → (1R,2R)-N1-(1-benzylpiperidin-3-yl)cyclohexane-1,2-diamine

HRID 2369966Notes

Reaction equation

HRID 2369966 reaction equation
O.Cl.[CH2:3]([N:10]1[CH2:15][CH2:14][CH2:13][C:12](=O)[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C([O-])(O)=O.[Na+].[C@@H:22]1([NH2:29])[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]1[NH2:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].FC(F)(F)C([O-])=O>C(Cl)Cl>[CH2:3]([N:10]1[CH2:15][CH2:14][CH2:13][CH:12]([NH:28][C@@H:23]2[CH2:24][CH2:25][CH2:26][CH2:27][C@H:22]2[NH2:29])[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 5

HCID 438061,2-Diaminocyclohexane, trans-HCID 84468TrifluoroacetateHCID 516892Sodium BicarbonateHCID 27608961-Benzylpiperidin-3-one hydrochloride hydrateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 71235672(1R,2R)-N1-(1-benzylpiperidin-3-yl)cyclohexane-1,2-diamineYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Benzyl-3-piperidone hydrochloride monohydrate (5.93 g, 26.3 mmol) was partitioned between a saturated aqueous NaHCO3 solution (30 ml) and CH2Cl2 (50 mL). The organic layer was separated and dried over Na2SO4 and filtered. The filtrated was collected and (1R,2R)-cyclohexane-1,2-diamine (3 g, 26.3 mmol) was added followed by sodium triacetoxy borohydride (8.35 g, 39.4 mmol). The reaction was stirred at rt overnight. After this time, the reaction was quenched with water (2 ml). The resulting solution was washed with saturated aqueous NaHCO3 (50 ml) and saturated NaCl (50 ml). The organic layer was dried over MgSO4, filtered and concentrated. The resulting residue was purified by RP Prep-HPLC. The desired fractions containing the product were concentrated to give the product, (1R,2R)—N1-(1-benzylpiperidin-3-yl)cyclohexane-1,2-diamine (3.01 g, 10.47 mmol, 40% yield) as a trifluoroacetate salt and as a white solid. 1H NMR (500 MHz, MeOH-d3) δ ppm 7.54-7.36 (m, 5H), 4.27-3.99 (m, 2H), 3.24-2.94 (m, 3H), 2.69 (d, J=9.90 Hz, 2H), 2.46-2.27 (m, 1H); 2.25-2.02 (m, 2H); 2.03-1.83 (m, 2H); 1.83-1.62 (m, 4H); 1.47-1.19 (m, 4H); 1.05 (d, J=11.55 Hz, 1H). 13C NMR (126 MHz, MeOH-d3) δ ppm 132.27, 130.75, 130.25, 62.31, 58.81, 56.46, 53.57, 32.76, 31.33, 25.99, 25.73, 25.40

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. customThe filtrated was collected
  5. customAfter this time, the reaction was quenched with water (2 ml)
  6. washThe resulting solution was washed with saturated aqueous NaHCO3 (50 ml) and saturated NaCl (50 ml)
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by RP Prep-HPLC
  11. additionThe desired fractions containing the product
  12. concentrationwere concentrated

Sources & evidence

ORD record
ord-4b5dbbe4bf7a43ed85228a357aa01f94
Source dataset
uspto-grants-2014_04
Patent number
US08710049B2

Reaction notes

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