反应详情

温度

35 °C

A 500-mL flask equipped with an N2 inlet/temperature probe, overhead stirrer and an addition funnel was charged with sodium amide (13.3 g, 327.3 mmol) and tetrahydrofuran (110 g) then warmed to 35° C. Through the addition funnel was slowly charged the tetrahydrofuran/toluene solution of Example 8 (35.57 g, 130.9 mmol). The addition funnel was rinsed with tetrahydrofuran (12 g). The reaction temperature was adjusted to 50° C. and the reaction was stirred for 3 hours before an HPLC sample was taken that showed the reaction was complete. In a separate flask equipped with an overhead stirred and a thermocouple was charged water (142 g), acetic acid (31.5 g) and toluene (54 g). The resulting mixture was then chilled to 0° C. The heterogeneous reaction mixture was quenched by addition to the acetic acid/toluene mixture while maintaining the temperature below 25° C. The reaction flask was rinsed with toluene (14 g) and water (14 g), which were added to the quench flask. The pH of the quench mixture was 6.04. The pH of the mixture was adjusted to 7.5 using 50% NaOH solution (11 g). The aqueous layer was extracted with 1:1 toluene/tetrahydrofuran (50 g). The organic layers were combined, filtered through a fritted glass filter and concentrated to a total volume of about 75 mL. The residue was diluted with toluene (125 g) and concentrated to a total volume of about 100 mL. Solid had formed during the distillations. The mixture was cooled to 0° C. and stirred for 1 hour. The mixture was filtered and the solid was washed with three portions of cold toluene and dried under vacuum to give the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.23 (s, 3H) 1.37-1.51 (m, 2H) 1.44 (s, 9H) 1.88-1.98 (m, 2H) 3.19-3.32 (m, 2H) 3.51-3.68 (m, 2H) 5.56-5.76 (m, 2H).

1. customA 500-mL flask equipped with an N2 inlet/temperature probe, overhead stirrer and an addition funnel
2. washThe addition funnel was rinsed with tetrahydrofuran (12 g)
3. customwas adjusted to 50° C.
4. customIn a separate flask equipped with an overhead
5. stirringstirred
6. additiona thermocouple was charged water (142 g), acetic acid (31.5 g) and toluene (54 g)
7. temperatureThe resulting mixture was then chilled to 0° C
8. customThe heterogeneous reaction mixture was quenched by addition to the acetic acid/toluene mixture
9. temperaturewhile maintaining the temperature below 25° C
10. washThe reaction flask was rinsed with toluene (14 g) and water (14 g), which
11. additionwere added to the quench flask
12. extractionThe aqueous layer was extracted with 1:1 toluene/tetrahydrofuran (50 g)
13. filtrationfiltered through a fritted glass
14. filtrationfilter
15. concentrationconcentrated to a total volume of about 75 mL
16. additionThe residue was diluted with toluene (125 g)
17. concentrationconcentrated to a total volume of about 100 mL
18. customSolid had formed during the distillations
19. temperatureThe mixture was cooled to 0° C.
20. stirringstirred for 1 hour
21. filtrationThe mixture was filtered
22. washthe solid was washed with three portions of cold toluene
23. customdried under vacuum