Dimethyl Sulfide → HCID 86623179, compound

Temperature

-60 °C

Chlorine gas (2469.6 mL, 118 mmol) was charged to toluene (373.3 mL, 16 rel vol) at −60° C. Dimethyl sulphide (11.67 mL, 121 mmol) was then added dropwise to the cooled solution over 30 minutes, keeping the contents at −60° C. After 30 minutes at this temperature, isopropyl 2-[(4R,6S)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxan4-yl}acetate (24.56 g, 95 mmol) in toluene (46.7 mL) was added dropwise to the vessel over 30 minutes, maintaining the internal temperature at −60° C. The reaction mixture was agitated at −60° C. for 30 minutes followed by the dropwise addition of triethylamine (26.36 g, 261 mmol) over 30 minutes, allowing the internal temperature to rise to −50° C. The reaction mixture was then allowed to warm to 25° C. evenly over 75 minutes. The resulting slurry was stirred at 25° C. for 30 minutes, then water (77 mL) was added and the mixture agitated for 30 minutes. The aqueous layer was separated and the pH checked (pH should be between 7.5 and 8.5). The resulting organic portion was washed with water (23.3 mL) and the organic portion separated for vacuum distillation at 150 mbar. Distillation was continued until ˜350 mL of toluene had been removed. Toluene (350 mL) was added to the flask and the vacuum distillation repeated at 150 mbar to remove ˜350 mL of toluene. The resulting solution was transferred to a flask containing activated 4 angstrom molecular sieves and left at ambient temperature overnight. This solution was used directly for the coupling stage.

1. customat −60° C
2. customto rise to −50° C
3. temperatureto warm to 25° C. evenly over 75 minutes
4. stirringThe resulting slurry was stirred at 25° C. for 30 minutes
5. stirringthe mixture agitated for 30 minutes
6. customThe aqueous layer was separated
7. washThe resulting organic portion was washed with water (23.3 mL)
8. customthe organic portion separated for vacuum distillation at 150 mbar
9. distillationDistillation
10. customhad been removed
11. additionToluene (350 mL) was added to the flask
12. distillationthe vacuum distillation
13. customto remove ˜350 mL of toluene
14. customThe resulting solution was transferred to a flask
15. additioncontaining
16. waitleft at ambient temperature overnight

ORD record

ord-8bd1d225a88941bea5ff67e486f3664d

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08063213B2