Dimethyl Sulfide → HCID 21869075, compound

Temperature

-5 °C

In a 3-necked, round bottom flask equipped with a mechanical stirrer 2-phenoxyaniline (37.0 g, 0.2 mol) was dissolved in dichloromethane (350 mL). A vigreux column was attached and part of the dichloromethane (100 mL) was distilled off. The reaction solution was then cooled to −5° C. using a dry ice/acetone bath. Dimethyl sulfide (18 mL, 0.25 mol) was added while the temperature of the reaction solution was maintained between −5 and 0° C. Then N-chlorosuccinimide (27.0 g, 0.2 mol) was added over a 10 minute period while the temperature of the reaction mixture was maintained between −5 and 0° C. After addition was complete, an ice/water bath was substituted for the dry ice/acetone bath to maintain the temperature near 0° C. while the reaction mixture was stirred for 30 minutes. Then triethylamine (60 mL, 0.42 mol) was added, and the mixture was heated at reflux for 2 hours. After the reaction mixture cooled to room temperature, a solution of sodium sulfite (20 g) in water (500 mL) was added to the stirred reaction mixture. After 10 minutes, the reaction mixture was decanted, and the organic layer was washed with water (500 mL). A 250 mL, 3-necked round bottom flask was fitted with a distillation head and an addition funnel. Part of the organic layer (100 mL) was poured into the flask, and the remainder of the organic layer was poured into the addition funnel. The organic layer material was added to the flask in 50 mL portions while solvent was removed by distillation. After all of the organic layer had been added and the flask temperature reached 110° C., the residual material was cooled to room temperature and diluted with cyclohexane (50 mL). The mixture was then heated to 60° C., and acetic anhydride (20 mL) was added over a 15 minute period. After the reaction mixture was held at 60° C. for one hour, it was cooled to room temperature and seeded with product crystals. After the mixture was stirred for one hour, the product was collected by filtration. The collected material was repeatedly washed with hexanes and petroleum ether and dried in vacuo to provide a crystalline product (24.41 g, 59% yield, 98% purity by gas chromatography area). This product was purified by recrystallization from toluene to afford product (13.24 g) that showed no impurity peaks by gas chromatography and 1H NMR.

1. distillationpart of the dichloromethane (100 mL) was distilled off
2. temperaturewas maintained between −5 and 0° C
3. temperaturewas maintained between −5 and 0° C
4. additionAfter addition
5. temperatureto maintain the temperature near 0° C. while the reaction mixture
6. temperaturethe mixture was heated
7. temperatureat reflux for 2 hours
8. temperatureAfter the reaction mixture cooled to room temperature
9. waitAfter 10 minutes
10. customthe reaction mixture was decanted
11. washthe organic layer was washed with water (500 mL)
12. customA 250 mL, 3-necked round bottom flask was fitted with a distillation head and an addition funnel
13. additionPart of the organic layer (100 mL) was poured into the flask
14. additionthe remainder of the organic layer was poured into the addition funnel
15. additionThe organic layer material was added to the flask in 50 mL portions while solvent
16. customwas removed by distillation
17. additionAfter all of the organic layer had been added
18. customreached 110° C.
19. temperaturethe residual material was cooled to room temperature
20. additiondiluted with cyclohexane (50 mL)
21. temperatureThe mixture was then heated to 60° C.
22. additionacetic anhydride (20 mL) was added over a 15 minute period
23. waitAfter the reaction mixture was held at 60° C. for one hour
24. temperatureit was cooled to room temperature
25. stirringAfter the mixture was stirred for one hour
26. filtrationthe product was collected by filtration
27. washThe collected material was repeatedly washed with hexanes and petroleum ether
28. customdried in vacuo
29. customto provide a crystalline product (24.41 g, 59% yield, 98% purity by gas chromatography area)
30. customThis product was purified by recrystallization from toluene

ORD record

ord-495ad5d1b7ee408ba7ab06671b85363c

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07145035B2