Azobisisobutyronitrile → 3-Bromo-2-(bromomethyl)-6-chloropyridine

To a stirred solution of 3-bromo-6-chloro-2-methylpyridine (105 g, 509 mmol) in CCl4 (2 L) was added N-bromosuccinimide (95 g, 534 mmol) followed by AIBN (8.35 g, 50.9 mmol). The reaction was brought to reflux for 24 hours and then cooled to r.t., filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with 60% methylene chloride/heptanes afforded semi-pure product. Further purification by SFC on a Chiralpak AD-H column with 20% IPA/CO2 [the conditions of the preparative separation were as follows: column Chiralpak AD-H (2.1×25 cm, 5 μm particle size) (Chiral Technologies, West Chester, Pa., USA); mobile phase 20% 2-propanol/CO2; elution mode isocratic pump-mixed; flow rate 50 mL/min; pressure 100 bar.] gave 3-bromo-2-(bromomethyl)-6-chloropyridine. LCMS=285.7 (M+H)+ 1H NMR (CDCl3, 500 MHz) δ 7.81 (d, J=8.4 Hz, 1H), 7.15 (d, J=8.3 Hz, 1H), 4.63 (s, 2H).

1. temperatureto reflux for 24 hours
2. filtrationfiltered
3. concentrationconcentrated
4. customPurification of the residue by flash chromatography on silica gel with 60% methylene chloride/heptanes afforded semi-pure product
5. customFurther purification by SFC on a Chiralpak AD-H column with 20% IPA/CO2 [
6. customthe conditions of the preparative separation
7. washelution mode isocratic pump-mixed

ORD-Eintrag

ord-b77012bee3804a04ac9f68a6629b36a8

Quelldatensatz

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09221834B2