Dichloromethane → 4-Fluorophenethyl alcohol methanesulfonate

Temperature

2.5 °C

A suitable reactor maintained under nitrogen was charged with 4-fluorophenethyl alcohol (2.6 kg, 18.6 mol) and 18 L of methylene chloride. The stirred solution was cooled to and maintained at 0-5° C. while triethylamine 2.85 kg (28.2 mol) was added fairly rapidly. The reaction temperature was maintained at 0-5° C. while adding methanesulfonyl chloride (2.5 kg, 21.8 mol) over 1 hour. The stirred reaction mixture was maintained at 0-5° C. for 1 hour, then it was warmed to room temperature within approximately 2 hours. The reaction mixture was diluted with a solution of 0.5 kg of 33% hydrochloric acid in 10 L of water. The organic phase was separated and washed with a solution of 0.2 kg of 33% hydrochloric acid in 5 L of water. Both acidic extracts were combined and extracted with 5 L of methylene chloride. Both organic phases were combined, washed with 2×15 L of water, then dried with sodium sulfate (2 kg). Drying agent was filtered off and washed with 2×5 L of methylene chloride. The majority of the solvent was boiled off at atmospheric pressure, with the final amount distilled off at 35° C./500 torr to give 4-fluorophenethyl alcohol methanesulfonate (4.17 kg.)

1. temperatureA suitable reactor maintained under nitrogen
2. temperatureThe stirred solution was cooled to and
3. additionwas added fairly rapidly
4. customThe stirred reaction mixture
5. temperaturewas maintained at 0-5° C. for 1 hour
6. temperatureit was warmed to room temperature within approximately 2 hours
7. customThe organic phase was separated
8. washwashed with a solution of 0.2 kg of 33% hydrochloric acid in 5 L of water
9. extractionextracted with 5 L of methylene chloride
10. washwashed with 2×15 L of water
11. dry with materialdried with sodium sulfate (2 kg)
12. customDrying agent
13. filtrationwas filtered off
14. washwashed with 2×5 L of methylene chloride
15. distillationwith the final amount distilled off at 35° C./500 torr

ORD record

ord-f2ed1e239bf64572844dd9fd847cfe67

Source dataset

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06713627B2