Acetaldehyde → HCID 68506452, compound

HRID 1715113Notes

Reaction equation

HRID 1715113 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([O:23][CH2:24][CH:25]=[CH2:26])=[O:22])=[CH:17][C:16]=2[NH2:27])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:28](=O)[CH3:29]>C(O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH2:24]([O:23][C:21]([C:18]1[CH:19]=[CH:20][C:15]2[N:14]([CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]3)[C:28]([CH3:29])=[N:27][C:16]=2[CH:17]=1)=[O:22])[CH:25]=[CH2:26]

Participants

5

Reactant 2

HCID 177AcetaldehydeHCID 68509550HCID 68509550, compound

Product 1

HCID 68506452HCID 68506452, compoundYield 45.1%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 702EthanolSolvent

Procedure

To a stirred solution of 4-(4-allyloxycarbonyl-2-amino-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (15.0 g, 39.95 mmol, 1.0 equiv) in ethanol (250 mL) were added copper(II) acetate (14.51 g, 79.90 mmol, 2.0 equiv) and acetaldehyde (44.1 mL, 0.20 mol, 5.0 equiv; 20% solution in water) and the reaction mixture heated to refluxe for 36 h. The solvent was evaporated, the residue diluted with water and extracted with ethyl acetate. The combined organic fractions were washed with water and a sat. solution of NaCl, dried over Na2SO4, concentrated by evaporation under reduced pressure and purified with silica column chromatography eluting with a gradient of hexane/ethyl acetate (3:7→1:9) to obtain 7.2 g (45%) of the title compound as a brown solid. 1H NMR (400 MHz, DMSO): δ 1.46 (s, 9H), 1.88-1.91 (m, 2H), 2.14-2.20 (m, 2H), 2.63 (s, 3H), 2.97 (br s, 2H), 4.13-4.15 (m, 2H), 4.58 (t, J=11.5 Hz, 1H), 4.81 (d, J=4.6 Hz, 2H), 5.28 (d, J=10.4 Hz, 1H), 5.40 (d, J=17.2 Hz, 1H), 6.03-6.10 (m, 1H), 7.68 (d, J=8.3 Hz, 1H), 7.81 (d, J=8.3 Hz, 1H), 8.14 (s, 1H). MS (ISP): 400.3 [M+H]+.

Workup

  1. temperaturethe reaction mixture heated
  2. customThe solvent was evaporated
  3. additionthe residue diluted with water
  4. extractionextracted with ethyl acetate
  5. washThe combined organic fractions were washed with water
  6. dry with materiala sat. solution of NaCl, dried over Na2SO4
  7. concentrationconcentrated by evaporation under reduced pressure
  8. custompurified with silica column chromatography
  9. washeluting with a gradient of hexane/ethyl acetate (3:7→1:9)

Sources & evidence

ORD record
ord-3f6c9501361940b790c9df409a1f3d72
Source dataset
uspto-grants-2010_09
Patent number
US07799806B2

Reaction notes

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