1-Chloro-3-iodopropane → 4-Chloro-3-(3-chloro-propyl)-2-fluoro-pyridine

Temperature

-78 °C

To a cooled (−78° C.) solution of 4-chloro-2-fluoro-pyridine (2.0 g, 15 mmol) in THF (15 mL) is added LDA solution (9.1 mL, 18 mmol, 2.0 M in THF). After the mixture is allowed to stir at −78° C. for 90 min, 1-chloro-3-iodo-propane (4.9 mL, 46 mmol) is added and the mixture is allowed to slowly warm to room temperature for 16 hrs. Then reaction is quenched with saturated NH4Cl and the mixture is extracted with DCM (3×). The combined organic layers are washed with brine, dried over Na2SO4 and concentrated to give the crude product. Purification by flash column chromatography affords 2.4 g of 4-chloro-3-(3-chloro-propyl)-2-fluoro-pyridine.

1. temperatureto slowly warm to room temperature for 16 hrs
2. customThen reaction
3. customis quenched with saturated NH4Cl
4. extractionthe mixture is extracted with DCM (3×)
5. washThe combined organic layers are washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customto give the crude product
9. customPurification by flash column chromatography

ORD record

ord-3e9fb5e82fe943d6abad776129d19283

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181272B2