Propylamine → HCID 54253268, compound

HRID 862206Notes

Reaction equation

HRID 862206 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7](=O)[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)=[N:9]O)=[CH:3][CH:2]=1.[CH2:22]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([CH:38]=O)[CH2:34][CH2:33]1)=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[CH2:40]([NH2:43])[CH2:41][CH3:42]>C(O)(=O)C>[CH2:22]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([C:38]2[N:43]([CH2:40][CH2:41][CH3:42])[C:7]([C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)=[C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=3)[N:9]=2)[CH2:34][CH2:33]1)=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 7852PropylamineHCID 2776272Benzyl 4-formylpiperidine-1-carboxylateHCID 73457808HCID 73457808, compound

Product 1

HCID 54253268HCID 54253268, compoundYield 23.7%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirring solution of 1-(pyridin-4-yl)-2-[3-(trifluoromethyl) phenyl]ethane-1,2-dione 2-oxime (83 mmol, 24.43 g), and 1-benzyloxycarbonyl-piperidine-4-carboxaldehyde [Amici et al Eur. J. Med. Chem. 26, 625-631 (1991)] (108 mmol, 26.7 g) in acetic acid (300 mL) was added propylamine (1.24 mol, 73.6 g) in a dropwise manner at ambient temperature. The reaction was heated to reflux for 3 h, cooled to ambient temperature and basified to pH8 with concentrated ammonium hydroxide/ice and extracted with ethyl acetate (3×500 mL). The combined organic layers were washed with brine dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was dissolved in methanol (100 mL) and treated with a solution of titanium trichloride (3×150 mL of 10-20 wt % in 20-30% HCl) and stirred for 18 h. The reaction was basified to pH 10 with saturated potassium carbonate and extracted with ethyl acetate (4×300 ml). The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was chromatographed on silica, eluting with a gradient of 30%-60% ethyl acetate:hexane to give a yellow oil which was rechromatographed on silica, eluting with a gradient of 25%-50% ethyl acetate:hexane to give 10.8 g of a pale yellow oil.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 3 h
  3. extractionextracted with ethyl acetate (3×500 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated under reduced pressure
  7. dissolutionThe residue was dissolved in methanol (100 mL)
  8. additiontreated with a solution of titanium trichloride (3×150 mL of 10-20 wt % in 20-30% HCl)
  9. extractionextracted with ethyl acetate (4×300 ml)
  10. washwashed with brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. customevaporated under reduced pressure
  13. customThe residue was chromatographed on silica
  14. washeluting with a gradient of 30%-60% ethyl acetate
  15. customhexane to give a yellow oil which
  16. customwas rechromatographed on silica
  17. washeluting with a gradient of 25%-50% ethyl acetate

Sources & evidence

ORD record
ord-8fffd904170b44aaac801119c1cd833a
Source dataset
uspto-grants-1998_02
Patent number
US05717100

Reaction notes

Loading…