Methanesulfonyl chloride → 6-Azidomethyl-2-chloro-nicotinic acid methyl ester

To a cold (0° C.) solution of 2-chloro-6-hydroxymethyl-nicotinic acid methyl ester (4.98 g, 24.8 mmol) in dichloromethane (161 mL) was added mesyl chloride (2.5 mL, 29.8 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 30 minutes. The mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium bicarbonate, water and brine. The organic phase was isolated, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was taken up in dimethylformamide (62 mL) and sodium azide (4.03 g, 62 mmol) added. After stirring at room temperature for 16 hours, the reaction mixture was cooled to 0° C., quenched with water (ca. 50 mL), and extracted three times with ethyl acetate. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was subjected to flash chromatography (Si-PPC, gradient 0% to 50%, ethyl acetate in hexane) to afford the title compound as a pale yellow oil (4.76 g, 85%). LCMS (method B): RT=3.22 min, [M+H]+=227.

1. washwashed with a saturated aqueous solution of sodium bicarbonate, water and brine
2. customThe organic phase was isolated
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. stirringAfter stirring at room temperature for 16 hours
7. temperaturethe reaction mixture was cooled to 0° C.
8. customquenched with water (ca. 50 mL)
9. extractionextracted three times with ethyl acetate
10. washThe combined organic extracts were washed with water and brine
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD record

ord-fd4b9ed787c2405a8ef2022c20a2c4c1

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07923456B2