反应详情

A mixture of ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate (2.0 kg, 91.2%, 10.98 moles), β-mercaptopropionic acid (1.165 kg, 10.98 moles), p-toluenesulfonic acid (ptsa) monchydrate (0.710 kg, 3.73 moles) and pyridine (0.304 kg, 3.84 moles) in toluene is heated to reflux temperature, heated at reflux temperatures for 7 hours using a Dean Stark trap for removal of water, allowed to cool to room temperature over a 17 hour period, cooled to 50° C., treated with trifluoroacetic anhydride (TFAA) (2.306 kg, 10.98 moles) at 50°-12° C., treated with methanesulfonic acid (0.053 kg, 0.55 moles), allowed to warm to room temperature, held at room temperature until reaction is complete by HPLC analysis and quenched with water. The phases are separated. The organic phase is washed with water and distilled to remove the toluene. The remaining pot residue is treated with isopropyl alcohol (1.89 kg), cooled to 45° C., treated with heptane (1.65 kg), and cooled to room temperature. The resultant mixture is filtered and the filtercake is washed sequentially with a 1:1 isopropanol:heptane mixture (0.735 kg) and heptane (1.37 kg). The washed filtercake is dried in vacuo to give he title product as a white crystalline solid, 0.931 kg (36% yield) 98.4% purity, identified by HPLC analysis.

1. temperatureis heated
2. temperatureto reflux temperature
3. temperatureheated
4. temperatureat reflux temperatures for 7 hours
5. customfor removal of water
6. temperaturecooled to 50° C.
7. temperatureto warm to room temperature
8. customheld at room temperature until reaction
9. customquenched with water
10. customThe phases are separated
11. washThe organic phase is washed with water
12. distillationdistilled
13. customto remove the toluene
14. additionThe remaining pot residue is treated with isopropyl alcohol (1.89 kg)
15. temperaturecooled to 45° C.
16. additiontreated with heptane (1.65 kg)
17. temperaturecooled to room temperature
18. filtrationThe resultant mixture is filtered
19. washthe filtercake is washed sequentially with a 1:1 isopropanol
20. customThe washed filtercake is dried in vacuo