1-Bromo-2-Chloroethane → HCID 58427734, compound

A suspension of 2-cyano-6-hydroxybenzothiazole (1.0 g, 5.68 mmol) in acetone (5 mL) was prepared in a 50-mL 2-necked round-bottomed flask fitted with a reflux condenser. Anhydrous potassium carbonate (1.57 g, 11.3 mmol) was added to the reaction mixture and the suspension turned to a yellow solution. Then 1-bromo-2-chloroethane (1.06 g, 0.56 mL, 7.38 mmol) was added by syringe and the reaction mixture was heated at reflux using a heated stir plate and oil bath. The reaction was monitored periodically by RP HPLC. After 5 hours the reaction appeared to be about 30% complete. Additional 1-bromo-2-chloroethane was added (2.84 mmol, 0.21 mL) and the reaction was refluxed overnight. HPLC analysis indicated the reaction was about 50% complete. Additional 1-bromo-2-chloroethane (2.84 mmol, 0.21 mL) and potassium carbonate (0.60 g, 4.37 mmol) were added and the reaction was refluxed for the rest of the day (about 7 h). The reaction was about 64% complete, and it was refluxed overnight. The next morning the reaction was found to be about 84% complete. Additional 1-bromo-2-chloroethane (2.84 mmol, 0.21 mL) and potassium carbonate (0.60 g, 4.37 mmol) were added and the reaction was refluxed for the rest of the day (about 7 h). At this point the reaction was about 92% complete. The reaction mixture was allowed to cool to room temperature and it was then filtered through glass fiber paper and rinsed with acetone. The filtrate was concentrated to give a yellow-brown solid. The crude solid (1.3 g) was purified on silica gel (100 g) using 4:1 heptane-ethyl acetate. Fractions containing product were pooled and concentrated to give 1.0 g (74%) of the desired product as an off-white solid. The structure was confirmed by 1H NMR analysis in DMSO-d6.

1. customwas prepared in a 50-mL 2-necked round-bottomed flask
2. customfitted with a reflux condenser
3. temperaturethe reaction mixture was heated
4. temperatureat reflux
5. temperaturethe reaction was refluxed overnight
6. temperaturethe reaction was refluxed for the rest of the day (about 7 h)
7. temperatureit was refluxed overnight
8. temperaturethe reaction was refluxed for the rest of the day (about 7 h)
9. filtrationit was then filtered through glass fiber paper
10. washrinsed with acetone
11. concentrationThe filtrate was concentrated
12. customto give a yellow-brown solid
13. customThe crude solid (1.3 g) was purified on silica gel (100 g)
14. additionFractions containing product
15. concentrationconcentrated

ORD record

ord-01068994ce0b426d8078f6a24ae00f9d

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08106052B2