Benzaldehyde → ethyl (2E)-3-{6-[(1-benzyl-4-piperidyl)amino]-5-chloro-3-pyridyl}acrylate

HRID 226338Notes

Reaction equation

HRID 226338 reaction equation
[ClH:1].Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]2[N:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][CH:11]=2)[CH2:5][CH2:4]1.CCN(CC)CC.[CH:30](=O)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[BH4-].[Na+]>CCO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH2:30]([N:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]2[N:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][C:11]=2[Cl:1])[CH2:5][CH2:4]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 86603643ethyl (2E)-3-[6-(4-piperidylamino)-3-pyridyl]acrylate dihydrochloride

Product 1

HCID 86603651ethyl (2E)-3-{6-[(1-benzyl-4-piperidyl)amino]-5-chloro-3-pyridyl}acrylate

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of ethyl (2E)-3-[6-(4-piperidylamino)-3-pyridyl]acrylate dihydrochloride (309 mg) in EtOH (5 ml) was added Et3N(0.921 ml), then benzaldehyde (0.117 ml) and titanium(IV) isopropoxide (0.463 ml), the mixture was stirred at 23° C. for 12 hours. To the mixture was added sodium borohydride, the mixture was stirred at 23° C. for 24 hours. The reaction mixture was poured into sat.NaHCO3aq. (20 ml)-AcOEt (20 ml), the insoluble material was removed by filtration, then the filtrate was extracted with ethyl acetate. The extracts were washed with water, dried over magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography eluted with 5% MeOH in dichloromethane to give ethyl (2E)-3-{6-[(1-benzyl-4-piperidyl)amino]-5-chloro-3-pyridyl}acrylate (328 mg).

Workup

  1. additionThe reaction mixture was poured into sat.NaHCO3aq
  2. custom(20 ml)-AcOEt (20 ml), the insoluble material was removed by filtration
  3. extractionthe filtrate was extracted with ethyl acetate
  4. washThe extracts were washed with water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography
  8. washeluted with 5% MeOH in dichloromethane

Sources & evidence

ORD record
ord-978f5b3880b14f6d8cf269b01c352acf
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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