Tetrahydrofuran → 5-(1-Bromoethyl)-2-fluoropyridine

Temperature

-10 °C

To a 250 mL round-bottomed flask was added 2-fluoro-5-formylpyridine (5.10 mL, 40.8 mmol), (Frontier Scientific), and tetrahydrofuran (100 mL, 1233 mmol). The solution was stirred at −10° C. using an ice bath and treated dropwise via addition funnel with methylmagnesium bromide (14.27 mL, 42.8 mmol), (Aldrich). After the addition, the ice bath was removed and the mixture was stirred at ambient temperature. After 30 minutes the reaction was complete. The mixture was stirred at −10° C. and treated dropwise via syringe with methanesulfonyl chloride (3.41 mL, 44.0 mmol), (Aldrich). After the addition, the water bath was removed and the mixture was stirred at ambient temperature and progress was followed with LC/MS. The reaction mixture was quenched with water (50 ml) and diluted with DCM (150 ml). The aqueous layer was extracted with DCM (3×50 mL) dried over sodium sulfate, filtered and concentrated in vacuum to give 5-(1-bromoethyl)-2-fluoropyridine (7.16 g, 35.1 mmol, 86% yield).

1. additionAfter the addition
2. customthe ice bath was removed
3. stirringthe mixture was stirred at ambient temperature
4. stirringThe mixture was stirred at −10° C.
5. additionAfter the addition
6. customthe water bath was removed
7. stirringthe mixture was stirred at ambient temperature
8. customThe reaction mixture was quenched with water (50 ml)
9. additiondiluted with DCM (150 ml)
10. extractionThe aqueous layer was extracted with DCM (3×50 mL)
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuum

ORD record

ord-179ad5c736704171a4492f4336d24279

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362241B2