反应详情

温度

26 °C

To a suspension of 82 g of 3-carboxypropyl triphenylphosphonium bromide in 407 mL of 1,2-diethoxyethane at 14° C. is added over 25 minutes 220 g of 20 wt % potassium tert-butoxide in tetrahydrofuran while maintaining the reaction mixture temperature at 24-28° C. The mixture is stirred for 1 hour, cooled to 10° C., and a solution of 52.5 g of 1-phenylmethoxycarbonyl-4-piperidone in 246 mL of methyl tert-butyl ether is added over 30 minutes while maintaining cooling. After addition is complete, the mixture is stirred at 12° C. for 10 minutes, then warmed to 20° C. and stirred for an additional 30 minutes. The reaction mixture is treated with 410 mL of 1N aqueous HCl for 10 minutes, diluted with 328 mL of methyl tert-butyl ether, and then the phases are separated. The organic phase is washed with 205 mL of water, then 210 mL of 1N aqueous NaOH. The NaOH layer, which contains the product, is collected separately, washed with three 189 g portions of ethyl acetate, acidified to pH 3.48 with concentrated HCl, then extracted with 189 mL of ethyl acetate. The ethyl acetate layer is separated, washed with 211 mL of water, then dried for 30 minutes over 10 g of MgSO4, filtered, and concentrated in vacuo. The oily residue (50.7 g) is crystallized from toluene/heptane to afford a total of 29.46 g (51% yield) of 3-(1-phenylmethoxycarbonyl-4-piperidinylmethylene)propanoic acid. Mass Spec: Mcalc. 303, M+1obsvd 304. 1H NMR: (δ vs TMS, CDCl3) 2.2, t (2H); 2.25, t (2H); 2.35, m (4H); 3.45, m (4H), 5.15, s (2H); 5.2, m (1H); 7.33, 2 (5H). 13C NMR (δ vs TMS, CDCl3) 22.43, 28.2, 34.26, 35.66, 44.88, 45.74, 67.20, 122.02, 127.83, 127.95, 128.45, 128.69, 128.90, 136.17, 136.72, 155.34, 178.39

1. temperaturecooled to 10° C.
2. temperaturewhile maintaining
3. temperaturecooling
4. additionAfter addition
5. stirringthe mixture is stirred at 12° C. for 10 minutes
6. temperaturewarmed to 20° C.
7. stirringstirred for an additional 30 minutes
8. customthe phases are separated
9. washThe organic phase is washed with 205 mL of water
10. customis collected separately
11. washwashed with three 189 g portions of ethyl acetate
12. extractionextracted with 189 mL of ethyl acetate
13. customThe ethyl acetate layer is separated
14. washwashed with 211 mL of water
15. dry with materialdried for 30 minutes over 10 g of MgSO4
16. filtrationfiltered
17. concentrationconcentrated in vacuo
18. customThe oily residue (50.7 g) is crystallized from toluene/heptane