反应详情

温度

0 °C

A 100-L, flask equipped with an overhead stirrer, a thermocouple and an addition funnel was charge with the product from Example 18 (2.1 kg, 6.08 mol), CH2Cl2 (32 L) and triethylamine (0.92 kg, 9.12 mol) and the solution was cooled to 0° C. Methanesulfonyl chloride (0.77 kg, 6.69 mol) was added through the addition funnel such that the internal temperature of the reaction remained below 5° C. The reaction was followed by HPLC until the starting material was consumed. 4 M HCl in dioxane (23 L, 91.2 mol) was added through the addition funnel such that the temperature remained below 10° C. The ice bath was removed and the solution was allowed to stir at room temperature for 2 hours. The reaction was concentrated to about 5 L. Dioxane (4 L) was added and the solution was concentrated to about 4 L. Tetrahydrofuran (27 L) was added followed by solid K2CO3 (2.1 kg, 15.2 mol). After stirring for 30 minutes, the reaction was cooled to 0° C. and water (18 L) was added such that the temperature remained below 15° C. After 20 minutes, the layers were separated. The aqueous layer was extracted with tert-butyl methyl ether (12 L). The combined organic layers contained 1.37 kg of product (99.9% yield) and were used directly in the next reaction.

1. customremained below 5° C
2. customwas consumed
3. customremained below 10° C
4. customThe ice bath was removed
5. concentrationThe reaction was concentrated to about 5 L
6. additionDioxane (4 L) was added
7. concentrationthe solution was concentrated to about 4 L
8. additionTetrahydrofuran (27 L) was added
9. stirringAfter stirring for 30 minutes
10. temperaturethe reaction was cooled to 0° C.
11. customremained below 15° C
12. waitAfter 20 minutes
13. customthe layers were separated
14. extractionThe aqueous layer was extracted with tert-butyl methyl ether (12 L)