3-(Chloromethyl)pyridine hydrochloride → 3-((3-Fluoro-4-nitrophenoxy)methyl)pyridine

3-Fluoro-4-nitrophenol (7.5 g) is added to a stirred suspension of sodium hydride (2.2 g, 60% dispersion in mineral oil) in DMF (50 mL). The mixture is stirred at ambient temperature for 30 minutes. To this mixture is added a solution prepared by the addition of sodium hydride (2.2 g, 60% dispersion in mineral oil) to a stirred suspension of 3-chloromethylpyridine hydrochloride (8.2 g) in DMF (50 mL). The resulting mixture is stirred at 90° C. for 16 hours then cooled to ambient temperature. The reaction mixture is concentrated in vacuo and the residue partitioned between dichloromethane (100 mL) and water (100 mL). The aqueous phase is extracted four times with dichloromethane (100 mL). The combined organic phases are washed with brine (100 mL), dried over magnesium sulphate, filtered and concentrated in vacuo to give an orange solid. Recrystallisation from ethyl acetate gives 3-(3-fluoro-4-nitrophenoxymethyl)pyridine (4.6 g) as pale orange/brown cystals.

1. additionTo this mixture is added a solution
2. stirringThe resulting mixture is stirred at 90° C. for 16 hours
3. temperaturethen cooled to ambient temperature
4. concentrationThe reaction mixture is concentrated in vacuo
5. customthe residue partitioned between dichloromethane (100 mL) and water (100 mL)
6. extractionThe aqueous phase is extracted four times with dichloromethane (100 mL)
7. washThe combined organic phases are washed with brine (100 mL)
8. dry with materialdried over magnesium sulphate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give an orange solid
12. customRecrystallisation from ethyl acetate

ORD record

ord-f90af2fb79e24150815d7617f3024e5c

Source dataset

uspto-grants-2001_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06211234B1