反应详情

Butyllithium in hexane (192 ml) was added dropwise at -70° C. under nitrogen to a solution of N-(1-methylethyl)-2-propanamine (43.4 ml) in tetrahydrofuran (400 ml) and the mixture was stirred for 30 minutes. A solution of intermediate (1) (0.236 mol) in tetrahydrofuran (50 ml) was added dropwise and the mixture was stirrred at -70° C. for 1 hour. Ethyl 1-methyl-4-piperidinecarboxylate (0.284 mol) in tetrahydrofuran (50 ml) was added and after the addition was completed, the mixture was stirred at -70° C. for 1 hour. The mixture was brought slowly to room temperature. The mixture was poured into water and extracted with 1,1'-oxybisethane/dichloromethane. The organic layer was dried (MgSO4) and evaporated. The residue (64.3 g) was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH/NH4OH 96/4/0.1 to 90/10/0.1) (35-70 μm). The pure fractions were collected and evaporated, yielding 29.55 g (41% ) of (1-methyl-4-piperidinyl)[2-[2-(3-thienyl)ethyl]-2H-1,2,4-triazol-3-yl]methanone (interm. 3);

1. waitthe mixture was stirrred at -70° C. for 1 hour
2. additionafter the addition
3. stirringthe mixture was stirred at -70° C. for 1 hour
4. customwas brought slowly to room temperature
5. extractionextracted with 1,1'-oxybisethane/dichloromethane
6. dry with materialThe organic layer was dried (MgSO4)
7. customevaporated
8. customThe residue (64.3 g) was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH/NH4OH 96/4/0.1 to 90/10/0.1) (35-70 μm)
9. customThe pure fractions were collected
10. customevaporated