Allyl bromide → HCID 178440933, compound

Temperature

-78 °C

n-Butyllithium (100 mL of a 1.6 M solution in hexanes, 160 mmol, 2.5 equiv) was added via cannula over 10 min to a solution of diisopropylamine (22.4 mL, 160 mmol, 2.5 equiv) in THF (600 mL) at −78° C. The resulting pale yellow solution was stirred at −78° C. for 5 min, then was warmed to 0° C. for an additional 5 min. 2-Hydroxy-6-methylnicotinonitrile (8) (8.58 g, 64.0 mmol, 1 equiv) was added as a solid in small portions over 15 min and the deep orange solution thus obtained was stirred for 1 h at 0° C. Allyl bromide (8.31 mL, 96.0 mmol, 1.5 equiv) was then added and the reaction mixture was warmed to 23° C., maintained at that temperature for 30 min, and was partitioned between 1.0 M HCl (300 mL) and EtOAc (2×250 mL). The combined organic layers were dried over Na2SO4 and were concentrated. The resulting orange solid was triturated with boiling Et2O (100 mL) and subsequently cooled to 23° C., then was filtered through a medium frit, washed with Et2O (2×50 mL) and air-dried to give a1 (6.42 g, 58%) as a tan solid: mp=122-125° C.; IR (KBr pellet, cm−1) 2223, 1654; 1H NMR (DMSO-d6) δ 2.32-2.37 (m, 2H), 2.62 (t, 2H, J=7.6), 4.96-5.06 (m, 2H), 5.69-5.83 (m, 1H), 6.23 (d, 1H, J=7.3), 8.03 (d, 1H, J=7.3), 12.55 (s, br, 1H); Anal. C10H10N2O·0.10H2O: C, H, N.

1. temperaturewas warmed to 0° C. for an additional 5 min
2. customthe deep orange solution thus obtained
3. stirringwas stirred for 1 h at 0° C
4. temperaturethe reaction mixture was warmed to 23° C.
5. temperaturemaintained at that temperature for 30 min
6. customwas partitioned between 1.0 M HCl (300 mL) and EtOAc (2×250 mL)
7. dry with materialThe combined organic layers were dried over Na2SO4
8. concentrationwere concentrated
9. customThe resulting orange solid was triturated with boiling Et2O (100 mL)
10. temperaturesubsequently cooled to 23° C.
11. filtrationwas filtered through a medium frit
12. washwashed with Et2O (2×50 mL)
13. customair-dried

ORD record

ord-f99e35adfdeb449bbede379cd17d02ad

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06514997B2