Triethylamine → Ethyl 1-benzyl-4-(3-methyl-1,2,4-triazol-1-yl)-piperidin-4-ylcarboxylate

HRID 1602329Notes

Reaction equation

HRID 1602329 reaction equation
Cl.Cl.[CH2:3]([N:10]1[CH2:15][CH2:14][C:13]([C:18]([O:20][CH2:21][CH3:22])=[O:19])([NH:16][NH2:17])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.C(=N)(OC)C.[CH2:29]([N:31](CC)[CH2:32]C)[CH3:30]>CO>[CH2:3]([N:10]1[CH2:11][CH2:12][C:13]([C:18]([O:20][CH2:21][CH3:22])=[O:19])([N:16]2[CH:32]=[N:31][C:29]([CH3:30])=[N:17]2)[CH2:14][CH2:15]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10313100Ethanimidic acid, methyl ester, hydrochloride (1:1)HCID 19610927HCID 19610927, compound

Product 1

HCID 15663649Ethyl 1-benzyl-4-(3-methyl-1,2,4-triazol-1-yl)-piperidin-4-ylcarboxylateYield 15.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of ethyl 1-benzyl-4-hydrazino-piperidin-4-ylcarboxylate dihydrochloride salt (D27, 3.0 g, 0.0086 mol) in methanol (100 ml) under nitrogen was treated with methyl acetimidate hydrochloride (940 mg, 0.0086 mol) and triethylamine (3.7 ml, 0.026 mol) and stirred at room temperature for 3 h. The solution was concentrated in vacuo at below 30° C. and the residue treated with triethylorthoformate (50 ml) and pyridine (5 ml) and the heterogenous mixture stirred for 18 h at room temperature, followed by heating under reflux for 1.5 h. The mixture was concentrated in vacuo and the residue treated with potassium carbonate solution (30 ml) and extracted with ethyl acetate (2×40 ml). The combined extracts were dried (Na2SO4) and concentrated in vacuo to leave a dark red oil, which was chromatographed on silica gel eluting initially with ether, then with 1:1 ethyl acetate/ether to afford the title compound (D30) as a yellow oil (430 mg, 15%).

Workup

  1. concentrationThe solution was concentrated in vacuo at below 30° C.
  2. additionthe residue treated with triethylorthoformate (50 ml) and pyridine (5 ml)
  3. stirringthe heterogenous mixture stirred for 18 h at room temperature
  4. temperatureby heating
  5. temperatureunder reflux for 1.5 h
  6. concentrationThe mixture was concentrated in vacuo
  7. additionthe residue treated with potassium carbonate solution (30 ml)
  8. extractionextracted with ethyl acetate (2×40 ml)
  9. dry with materialThe combined extracts were dried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customto leave a dark red oil, which
  12. customwas chromatographed on silica gel eluting initially with ether

Sources & evidence

ORD record
ord-3b0e0445f0cb4522a609d28344611abd
Source dataset
uspto-grants-1999_11
Patent number
US05981545

Reaction notes

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