反应详情

In a 10 mL oven-dried flask was added Mg turnings (97 mg, 4.1 mmol) which was activated by the use of a heat-gun under vacuum. Under inert atmosphere was added a suspension of 2-iodo-toluene (380 mL, 3.0 mmol) in Et2O (3 mL) and the reaction mixture was allowed to reflux for 1 hours. A suspension of 4-piperidin-1-yl-butanenitrile 10 (Dahlbom et. al. Acta. Chem. Scand. 1951, 5, 690-697) (0.305 mg, 2.0 mmol) in CH2Cl2 (3 mL) was added via a syringe and the reaction mixture was stirred at rt overnight. The reaction mixture was quenched by addition of H2SO4 (10 mL, 2 M) and stirred at rt for 12 hours followed by addition of NaOH (12 mL, 2 M). Addition of THF (15 mL) was followed by extraction with ethyl acetate (3×50 mL), and the combined organic phases are washed with brine (10 mL) and NaOH (10 mL, 2 M), and dried (MgSO4) and evaporated to dryness to produce 0.21 g of crude 11. The crude product was subjected to preparative HPLC [eluent: Buffer A: 0.1% TFA; Buffer B: 80% CH3CN+0.1%TFA] to produce an analytically pure sample of compound 11; LC-MS [M+H]+ 245 (cald. 245.2).

1. customIn a 10 mL oven-dried flask
2. temperaturea heat-gun under vacuum
3. additionUnder inert atmosphere was added
4. temperatureto reflux for 1 hours
5. additionwas added via a syringe
6. customThe reaction mixture was quenched by addition of H2SO4 (10 mL, 2 M)
7. stirringstirred at rt for 12 hours
8. additionfollowed by addition of NaOH (12 mL, 2 M)
9. additionAddition of THF (15 mL)
10. extractionwas followed by extraction with ethyl acetate (3×50 mL)
11. washthe combined organic phases are washed with brine (10 mL) and NaOH (10 mL, 2 M)
12. dry with materialdried (MgSO4)
13. customevaporated to dryness
14. customto produce 0.21 g of crude 11