反应详情

温度

0 °C

Under an inert atmosphere, e.g., nitrogen, a reactor was charged with 1,3-propanediol (4.07 kg) and NMP (30 L). The reaction was cooled to −5 to 5° C. and kept under a nitrogen atmosphere. Sodium hydride (1.07 kg, 60% in mineral oil) was cautiously added portion-wise. After the addition was complete, the reaction was stirred at room temperature for an additional 2 hours. A solution of hexadecyl methanesulfonate 4 (4.39 kg) dissolved in NMP (10 L) was added slowly to the reaction mixture at 20 to 55° C. The resulting solution was stirred for 12 to 28 hours at 20 to 35° C. The reaction was monitored by GC-MS and was considered complete when the conversion rate was ≧95%. The reaction mixture was cooled down to −5 to 5° C. and slowly diluted with water (15 L). The reaction was extracted with ethyl acetate (2×25 L). The organic phase was washed with water (20 L), dried over Na2SO4 and concentrated to give a brown oil. The crude product was dissolved in methanol (20 L) and aged at 20 to 30° C. for 12 hours. The resulting solid impurities were filtered and discarded and the filtrate was concentrated. Acetonitrile (40 L) was added to the concentrate and the mixture was aged 5 to 15° C. for 16 hours. The solid was filtered and dried at 25 to 30° C. to afford 5 as a white solid (3.1 kg, 77%). Typical HPLC (AUC) purity was >95%. 1H-NMR was consistent with structure.

1. additionAfter the addition
2. additionwas added slowly to the reaction mixture at 20 to 55° C
3. stirringThe resulting solution was stirred for 12 to 28 hours at 20 to 35° C
4. temperatureThe reaction mixture was cooled down to −5 to 5° C.
5. extractionThe reaction was extracted with ethyl acetate (2×25 L)
6. washThe organic phase was washed with water (20 L)
7. dry with materialdried over Na2SO4
8. concentrationconcentrated
9. customto give a brown oil
10. waitaged at 20 to 30° C. for 12 hours
11. filtrationThe resulting solid impurities were filtered
12. concentrationthe filtrate was concentrated
13. additionAcetonitrile (40 L) was added to the
14. concentrationconcentrate
15. waitthe mixture was aged 5 to 15° C. for 16 hours
16. filtrationThe solid was filtered
17. customdried at 25 to 30° C.