反应详情

温度

12 °C

To a suspension of 4-(4-acetoxy-but-2-ynyloxy)-benzenesulfonic acid, sodium salt from Example 6 (360 g, 1.18 mol) in 2.1 L of dichloromethane in a 5-L 4-neck flask, was added N,N-dimethylformamide (14 g, 0.19 mol) and water (4.5 g, 0.25 mol). The mixture was cooled to 12° C. Oxalyl chloride (165 mL, 240 g, 1.89 mol) was added over 70 min while the temperature was maintained at 10–20° C. The mixture was slowly warmed to 23° C. over 1 h and stirred at this temperature for 1 h. The reaction was monitored for completion by HPLC (S.M. <3%). The mixture was quenched into 2 L of water in a 12-L flask at 30° C. After 5 min of stirring, the phases were separated and the organic phase was washed with water (1 L). The mixture was held at 0–5° C. overnight, resulting in clear phase separation. Dichloromethane was distilled off to a residual volume of about 700 mL. t-Butyl methyl ether (1.5 L) was added. Distillation was continued to a residual volume of 850 mL. The solution was cooled to 18° C. and seeded with crystals. After 35 min of stirring, product crystals formed. Heptane (650 mL) was added over 40 min while the temperature was maintained at 15–20° C. The mixture was heated to 35° C. to dissolve the product before it was cooled back to 20° C. More heptane (350 mL) was added over 10 min. The mixture was stirred at 15–20° C. for 40 min. The crystals were filtered in a funnel and washed with heptane (400 mL). The product was dried in vacuo at 23° C. to a constant weight (316 g, 89% yield). 1H NMR (300 MHz, CDCl3) δ 8.01 (m, 2H), 7.12 (m, 2H), 4.86 (t, J=1.8 Hz, 2H), 4.72 (t, J=1.8 Hz, 2H), 2.10 (s, 3H); 13C NMR (75 MHz, CDCl3) ppm 170.5, 163.0, 137.2, 129.9, 116.0, 83.3, 80.2, 56.8, 52.3, 21.0.

1. temperaturewas maintained at 10–20° C
2. temperatureThe mixture was slowly warmed to 23° C. over 1 h
3. customThe mixture was quenched into 2 L of water in a 12-L flask at 30° C
4. stirringAfter 5 min of stirring
5. customthe phases were separated
6. washthe organic phase was washed with water (1 L)
7. waitThe mixture was held at 0–5° C. overnight
8. customresulting in clear phase separation
9. distillationDichloromethane was distilled off to a residual volume of about 700 mL
10. additiont-Butyl methyl ether (1.5 L) was added
11. distillationDistillation
12. temperatureThe solution was cooled to 18° C.
13. stirringAfter 35 min of stirring
14. customproduct crystals formed
15. temperaturewas maintained at 15–20° C
16. temperatureThe mixture was heated to 35° C.
17. dissolutionto dissolve the product before it
18. temperaturewas cooled back to 20° C
19. stirringThe mixture was stirred at 15–20° C. for 40 min
20. filtrationThe crystals were filtered in a funnel
21. washwashed with heptane (400 mL)
22. customThe product was dried in vacuo at 23° C. to a constant weight (316 g, 89% yield)