Ammonia → 5-Bromo-2-chloro-3-nitropyridine

Temperature

0 °C

2-Amino-5-bromo-3-nitropyridine (21.8 g, 0.1 mol) was ground to a fine powder using a mortar and pestle and then suspended in 6M hydrochloric acid (250 ml). This mixture was cooled to 0° C. and treated with solid NaNO2 (8.3 g, 0.12 mol) at such a rate that the internal temperature remained below 5° C. (ca. 45 minutes). Following the addition, stirring at 0° C. was continued for a further 1 hour. To the resultant suspension was added a solution of freshly prepared copper(I) chloride (12.9 g. 0.13 mol) in degassed 38% hydrochloric acid and the reaction stirred to ambient temperature over 90 minutes before heating the reaction to 70° C. to complete the decomposition of the diazonium salt. The reaction was cooled, diluted with water (750 ml) and then air was passed through the mixture for 30 minutes before adding 0.88 ammonia to ca. pH 9. The blue mixture was shaken with diethyl ether (600 ml) and any remaining solids removed by filtration. The organic layer was then washed with 5% aqueous ammonia, water, brine and dried over anhydrous sodium sulphate. This solution was filtered and then pre-adsorbed on to silica. Purification by dry flash chromatography eluting with isohexane and a gradient of ethyl acetate from 5% to 20% gave 5-bromo-2-chloro-3-nitropyridine as a pale yellow solid (13.1 g, 55%) followed by recovered starting material (6.4 g); δH (400 MHz, CDCl3) 8.36 (1H, d, J 1, H-6), 8.69 (1H, d, J 1, H-4).

1. customremained below 5° C.
2. custom(ca. 45 minutes)
3. additionthe addition
4. stirringthe reaction stirred to ambient temperature over 90 minutes
5. temperaturebefore heating
6. customthe reaction to 70° C.
7. temperatureThe reaction was cooled
8. waitair was passed through the mixture for 30 minutes
9. customany remaining solids removed by filtration
10. washThe organic layer was then washed with 5% aqueous ammonia, water, brine
11. dry with materialdried over anhydrous sodium sulphate
12. filtrationThis solution was filtered
13. customPurification
14. customby dry flash chromatography
15. washeluting with isohexane

ORD record

ord-b1a52f95088e4339bd1baed1eb2177ed

Source dataset

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06723735B1