Citric Acid → (1R,2S)-1-Homopiperidin-2-yl-2-dibenzylamino-3-phenylpropan-1-ol

HRID 1436733Notes

Reaction equation

HRID 1436733 reaction equation
[CH2:1]([N:8]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@@H:9]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C@@H:10]([CH:12]1[NH:18][C:17](=O)[CH:16]=[CH:15][CH2:14][CH2:13]1)[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(OCC)(=O)C>C1COCC1.C(OCC)C>[NH:18]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH:12]1[C@@H:10]([OH:11])[C@@H:9]([N:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 311Citric AcidHCID 8857Ethyl AcetateHCID 690155047-((1R,2S)-2-dibenzylamino-1-hydroxy-3-phenylpropyl)-1,5,6,7-tetrahydroazepin-2-one

Product 1

HCID 69017466(1R,2S)-1-Homopiperidin-2-yl-2-dibenzylamino-3-phenylpropan-1-olYield 40%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve 7-((1R,2S)-2-dibenzylamino-1-hydroxy-3-phenylpropyl)-1,5,6,7-tetrahydroazepin-2-one (Isomer 1) (40 mg, 0.09 mmol) in THF (5 mL) and add BH3SMe2 (2 M in diethyl ether, 0.14 mL, 0.27 mmol). Stir the reaction at 50° C. for 3 hour. Add saturated aqueous citric acid (10 mL). Extract aqueous twice with ethyl acetate, combine organics and wash with saturated sodium chloride, dry (magnesium sulfate) and concentrate under reduced pressure. Add 20% palladium hydroxide on carbon (90 mg) and methanol (10 mL) and stir under 1 atmosphere of hydrogen overnight. Filter and evaporate to give a foam. Purify the product using a SCX column to give a thick residue (0.007 g, 40%).

Workup

  1. customthe reaction at 50° C. for 3 hour
  2. washwash with saturated sodium chloride
  3. dry with materialdry (magnesium sulfate)
  4. concentrationconcentrate under reduced pressure
  5. additionAdd 20% palladium hydroxide on carbon (90 mg) and methanol (10 mL)
  6. stirringstir under 1 atmosphere of hydrogen overnight
  7. filtrationFilter
  8. customevaporate
  9. customto give a foam
  10. customPurify the product

Sources & evidence

ORD record
ord-c19e1879c7c94385a06f50483365685d
Source dataset
uspto-grants-2009_11
Patent number
US07618978B2

Reaction notes

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