反应详情

A solution of bis(dibenzylidineacetone)palladium (1.438 g, 2.5 mmol) and 1,4-bis(diphenylphosphino)butane (1.066 g, 2.5 mmol) in tetrahydrofuran (20 mL) was stirred under nitrogen at room temperature for 15 min, then added via syringe to a stirred solution under nitrogen of 4-((alpha-S)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)benzyl)-N,N-diethylbenzamide (20.98 g, 50 mmol) and thiosalicylic acid (9.25 g, 60 mmol) in anhydrous tetrahydrofuran (100 mL). The reaction mixture was stirred under nitrogen for 2 h at room temperature, then evaporated to dryness, the residue dissolved ethyl acetate (120 mL) and diluted with ether (300 mL). The solution was washed with dilute sodium carbonate solution (saturated:H2O, 1:3, 3×200 mL). The organic solution was diluted with pentane (800 mL) and extracted with 3M-hydrochloric acid (5×40 mL), followed by M-hydrochloric acid (3×50 mL, alternating with water (3×50 mL)). The combined aqueous extracts were filtered to remove a small amount of suspended solid and the pH adjusted to 12 with 5-M NaOH. The resulting oily suspension was extracted with methylene chloride (3×150 mL), the combined organic extracts dried over anhydrous sodium sulfate and evaporated to dryness to yield 4-((alpha-S)-alpha-((2S,5R)-2,5-dimethyl-1-piperazinyl)benzyl)-N,N-diethylbenzamide as a very pale yellow solid (18.07 g, 97.8%). The product showed a single spot on thin layer chromatography (silica gel, EM60F264, 4% NH4OH/10% EtOH in ethyl acetate, Rf=0.25). and was used without further purification. Calc. for C24H33N3O 0.2 H2O: C, 75.24; H, 8.79; N, 10.97. Found C, 75.24; H, 8.87; N, 10.86%.

1. customevaporated to dryness
2. dissolutionthe residue dissolved ethyl acetate (120 mL)
3. additiondiluted with ether (300 mL)
4. washThe solution was washed with dilute sodium carbonate solution (saturated:H2O, 1:3, 3×200 mL)
5. additionThe organic solution was diluted with pentane (800 mL)
6. extractionextracted with 3M-hydrochloric acid (5×40 mL)
7. filtrationThe combined aqueous extracts were filtered
8. customto remove a small amount of suspended solid
9. extractionThe resulting oily suspension was extracted with methylene chloride (3×150 mL)
10. dry with materialthe combined organic extracts dried over anhydrous sodium sulfate
11. customevaporated to dryness