Benzaldehyde → racemic 8-(1-benzylpiperidin-4-yl)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine

HRID 546713Notes

Reaction equation

HRID 546713 reaction equation
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][O:10][C:11]1[CH:12]=[C:13](/[CH:23]=[CH:24]/[C:25]2[N:39]=[C:28]3[CH:29]([CH:33]4[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]4)[CH2:30][CH2:31][CH2:32][N:27]3[N:26]=2)[CH:14]=[CH:15][C:16]=1[N:17]1[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]1.[Na].C(=O)(O)[O-].[Na+]>C1COCC1.C(OCC)(=O)C.C(O)(=O)C>[CH2:1]([N:36]1[CH2:37][CH2:38][CH:33]([CH:29]2[CH2:30][CH2:31][CH2:32][N:27]3[N:26]=[C:25](/[CH:24]=[CH:23]/[C:13]4[CH:14]=[CH:15][C:16]([N:17]5[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]5)=[C:11]([O:10][CH3:9])[CH:12]=4)[N:39]=[C:28]23)[CH2:34][CH2:35]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 240BenzaldehydeHCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 668394842-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(piperidin-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine

Product 1

HCID 66839015racemic 8-(1-benzylpiperidin-4-yl)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Benzaldehyde (15 μl) and glacial acetic acid (16 μl) were added to a solution of racemic 2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(piperidin-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine obtained in Examples 118 and 119 (30 mg) in THF (2 ml), and the reaction solution was stirred at room temperature for 30 minutes. Sodium triacetoxyhydroborate (46 mg) was added to the reaction solution, and the reaction solution was stirred at room temperature for four hours. A saturated sodium bicarbonate solution and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Chromatorex™ NH; elution solvent: ethyl acetate) to obtain 27 mg of racemic 8-(1-benzylpiperidin-4-yl)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine. Then, the racemate was separated by CHIRALPAK™ IB manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm; mobile phase: 50% ethanol-hexane) to obtain the title optically active compound with a retention time of 14 minutes and positive optical rotation (9.4 mg; >99% ee) and the title optically active compound with a retention time of 20 minutes and negative optical rotation (8.9 mg; 99% ee).

Workup

  1. stirringthe reaction solution was stirred at room temperature for four hours
  2. customthe organic layer was separated
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (carrier: Chromatorex™ NH; elution solvent: ethyl acetate)

Sources & evidence

ORD record
ord-c095053b9bb34696a08b5dc17f7e087d
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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