Trifluoroacetic anhydride → (3-Bromo-6-chloro-4-methylpyridin-2-yl)methanol

To a solution of 3-bromo-6-chloro-2,4-dimethylpyridine 1-oxide (28.7 g, 121 mmol) in CH2Cl2 (240 mL) was added trifluoracetic anhydride (240 mL, 1699 mmol). The reaction was stirred for 3 hours at room temperature and then concentrated. The residue was dissolved in MeOH (1.7 L) and cooled to 0° C. 1M K2CO3 (360 mL, 360 mmol) was added dropwise, and the reaction was stirred for 10 minutes at 0° C. and then warmed to r.t. for 1 hour. The reaction was then concentrated to a volume of 300 mL and diluted with EtOAc (1 L). Water (1 L) was added and the layers were separated. The aqueous layer was extracted with additional EtOAc (2×1 L). The organic layers were combined, washed with brine (1 L), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with 0 to 75% EtOAc/heptanes afforded (3-bromo-6-chloro-4-methylpyridin-2-yl)methanol. LCMS=236.1 and 238.1 (M+H)+ 1H NMR (CDCl3, 500 MHz) δ 7.17 (s, 1H), 4.73 (s, 2H), 2.42 (s, 3H).

1. concentrationconcentrated
2. dissolutionThe residue was dissolved in MeOH (1.7 L)
3. temperaturecooled to 0° C
4. stirringthe reaction was stirred for 10 minutes at 0° C.
5. temperaturewarmed to r.t. for 1 hour
6. concentrationThe reaction was then concentrated to a volume of 300 mL
7. additiondiluted with EtOAc (1 L)
8. additionWater (1 L) was added
9. customthe layers were separated
10. extractionThe aqueous layer was extracted with additional EtOAc (2×1 L)
11. washwashed with brine (1 L)
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated
15. customPurification of the residue by flash chromatography on silica gel with 0 to 75% EtOAc/heptanes

ORDレコード

ord-46d95b2c96684b6da2eeb4f9140369cb

出典データセット

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09221834B2