Methyl chloroformate → (5-Chloropyridin-3-yl)methanol

To a solution of 5-chloro-nicotinic acid (2 g, 12.7 mmol) and TEA (1.52 g, 15 mmol) in THF (30 mL) was added slowly methyl chloroformate (1.42 g, 15 mmol) at 0° C. The resulting mixture was stirred at room temperature overnight. The reaction was diluted with ethyl acetate, washed with saturated ammonia chloride and dried over anhydrous sodium sulfate. The organic layer was concentrated to give the crude product (2.8 g, crude), which was dissolved in THF (40 mL) and cooled to −78° C. Lithium aluminium hydride (570 mg, 15 mmol) was added portion-wise. The resulting mixture was stirred for 30 min. The reaction was quenched with aqueous sodium hydroxide and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated to give the crude product, which was purified by silica gel column chromatography (30% ethyl acetate in petroleum ether) to afford the title compound (1.4 g, 9.72 mmol, 76% yield). MS (ESI) m/z 144.1 [M+H]+.

1. washwashed with saturated ammonia chloride
2. dry with materialdried over anhydrous sodium sulfate
3. concentrationThe organic layer was concentrated
4. customto give the crude product (2.8 g, crude), which
5. temperaturecooled to −78° C
6. stirringThe resulting mixture was stirred for 30 min
7. customThe reaction was quenched with aqueous sodium hydroxide
8. extractionextracted with ethyl acetate
9. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
10. concentrationconcentrated
11. customto give the crude product, which
12. customwas purified by silica gel column chromatography (30% ethyl acetate in petroleum ether)

ORD record

ord-85172c0429ba4df18d15ba76afb7e519

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156798B2