1-Phenethylamine, (-)- → (E)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]-1-[(1S)-1-phenylethyl]piperidin-2-one

HRID 1362643Notes

Reaction equation

HRID 1362643 reaction equation
C(O[C:4](=[O:25])/[C:5](=[CH:10]/[C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]2)=[C:13]([O:23][CH3:24])[CH:12]=1)/[CH2:6][CH2:7][CH:8]=O)C.[CH3:26][C@H:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.C(O)(=O)C.C(Cl)Cl>[CH3:24][O:23][C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][C:14]=1[N:17]1[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]1)/[CH:10]=[C:5]1/[C:4](=[O:25])[N:34]([C@H:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH3:26])[CH2:8][CH2:7][CH2:6]/1

Participants

8

Reactant 4

HCID 758181-Phenethylamine, (-)-HCID 5049666Sodium triacetoxyborohydrideHCID 86585896Sodium bicarbonate water2×HCID 86602475(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]-5-oxovaleric acid ethyl ester

Product 1

HCID 54765774(E)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]-1-[(1S)-1-phenylethyl]piperidin-2-one

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a methylene chloride (2 mL) solution of (E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]-5-oxovaleric acid ethyl ester (162 mg), (S)-(−)-alpha-methylbenzylamine (183 μL), acetic acid (1.0 mL) and sodium triacetoxy borohydride (120 mg) were added one by one. After agitating reaction solution at room temperature overnight, a saturated sodium bicarbonate water and ethyl acetate were added to the reaction solution, and the organic layer was partitioned. After the obtained organic layer was washed with a saturated saline solution, it was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was dissolved in acetic acid (2 mL), and heat-refluxing of the reaction solution was carried out overnight. After cooling reaction solution to 0° C., neutralized with a saturated sodium bicarbonate water, ethyl acetate was added to the reaction solution, and the organic layer was partitioned. After the obtained organic layer was washed with a saturated saline solution, it was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate=1:1->ethyl acetate: ethanol=10:1), and 13.7 mg of the title compound was obtained. The physical properties of the compound are as follows.

Workup

  1. customreaction solution at room temperature overnight
  2. customthe organic layer was partitioned
  3. washAfter the obtained organic layer was washed with a saturated saline solution, it
  4. dry with materialwas dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe obtained residue was dissolved in acetic acid (2 mL)
  7. temperatureheat-refluxing of the reaction solution
  8. temperatureAfter cooling
  9. customreaction solution to 0° C.
  10. additionwas added to the reaction solution
  11. customthe organic layer was partitioned
  12. washAfter the obtained organic layer was washed with a saturated saline solution, it
  13. dry with materialwas dried over anhydrous magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate=1:1->ethyl acetate: ethanol=10:1)

Sources & evidence

ORD record
ord-326e4c204caf44c588f79be8265f82e9
Source dataset
uspto-grants-2011_02
Patent number
US07880009B2

Reaction notes

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