Formaldehyde → HCID 54098525, compound

HRID 376856Notes

Reaction equation

HRID 376856 reaction equation
[C:1]([O:5][C:6](=[O:30])[CH:7]([CH:11]([C:22]([N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)=[O:23])[CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)[C:8](O)=O)([CH3:4])([CH3:3])[CH3:2].N1CCCCC1.C=O>C(O)C>[C:1]([O:5][C:6](=[O:30])[C:7]([CH:11]([C:22]([N:24]1[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1)=[O:23])[CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)=[CH2:8])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 8082PiperidineHCID 545078142-[4-(4-Chloro-phenyl)-1-(piperidine-1-carbonyl)-butyl]-malonic acid tert-butyl ester

Product 1

HCID 54098525HCID 54098525, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

2-[4-(4-Chloro-phenyl)-1-(piperidine-1-carbonyl)-butyl]-malonic acid tert-butyl ester (2.0 g, 4.6 mmol) was dissolved in ethanol (100 ml) and treated with piperidine (0.43 ml, 5.5 mmol) and 37% w/w formaldehyde (1.9 ml, 23 mmol). The reaction mixture was heated at 50° C. overnight. The solvent was removed under reduced pressure, the residue was dissolved in ethyl acetate (60 ml), and the solution was washed with water (3×30 ml), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 20% ethyl acetate in hexane) to give the 2-[4-(4-Chloro-phenyl)-1-(piperidine-1-carbonyl)-butyl]-acrylic acid tert-butyl ester as a colourless oil (750 mg, 41%). 1H-NMR: δ (CDCl3), 7.21 (2H, d, J=8.4 Hz), 7.09 (2H, d, J=8.4 Hz), 6.19 (1H, s), 5.71 (1H, s), 3.82 (1H, dd, J=4.9, 8.2 Hz), 3.64 (1H, m), 3.51-3.32 (3H, m), 2.67-2.50 (2H, m), 1.90 (1H, m), 1.61-1.38 (9H, m) and 1.48 (9H, s).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in ethyl acetate (60 ml)
  3. washthe solution was washed with water (3×30 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (silica gel, 20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-1cb81459b6f143fa814ae7a364b029b8
Source dataset
uspto-grants-2000_02
Patent number
US06022873

Reaction notes

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