Isoamyl Nitrite → HCID 67389334, compound

Temperature

-10 °C

4-Bromo-6-ethyl-2-ethylsulfanyl-pyridin-3-ylamine (476 mg, 1.82 mmoles) was dissolved into EtOH (5 mL) and chilled to −10° C. under nitrogen. At −10° C. 48% wt. aq. HBF4 (1.0 mL) was added and the temperature was further lowered to −25° C. At −25° C. isoamyl nitrite (0.256 mL, 1.9 mmoles) was slowly added (over 1 min), and the temperature was allowed to warm to −5° C. The reaction was stirred at −5° C. for 30 min. After this period the reaction mix was chilled to −25° C. and an excess of 50% aqueous H3PO2 (5.0 mL) was added. The mix was then allowed to warm to ambient temperature and was stirred at this temperature for 1 hour (vigorous bubbling is observed). After this period the reaction was combined with 40 mL of diethyl ether followed (carefully) by saturated NaHCO3 (10 mL). The mix was then extracted with diethyl ether (2×20 mL) and the resultant ether layer was washed with brine. After drying over anhydrous MgSO4 the ethereal layer was evaporated in vacuo to yield crude product. The crude product was purified using flash silica chromatography (0-10% EtOAc/Hexane) to yield 4-bromo-2-ethylsulfanyl-6-ethylpyridine (340 mg, 76%) as a golden-yellow liquid. 1H-NMR (CDCl3): δ 7.09 (br d, J=1.3 Hz, 1H), 6.90 (br d, J=1.5 Hz, 1H), 3.0 (q, J=7.3 Hz, 2H), 2.73 (q, J=7.6 Hz, 2H), 1.39 (t, J=7.3 Hz, 3H), 1.27 (t, J=7.6 Hz, 3H).

1. customAt −10° C
2. customwas further lowered to −25° C
3. temperatureto warm to −5° C
4. additionAfter this period the reaction mix
5. temperaturewas chilled to −25° C.
6. temperatureto warm to ambient temperature
7. stirringwas stirred at this temperature for 1 hour
8. custom(vigorous bubbling is observed)
9. waitAfter this period the reaction was combined with 40 mL of diethyl ether
10. extractionThe mix was then extracted with diethyl ether (2×20 mL)
11. washthe resultant ether layer was washed with brine
12. dry with materialAfter drying over anhydrous MgSO4 the ethereal layer
13. customwas evaporated in vacuo
14. customto yield crude product
15. customThe crude product was purified

ORD record

ord-7b1cc59d6a2749e1a803fe2abe698d2f

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08013001B2