Methanamine, N-methoxy-, hydrochloride (1:1) → (e)-3-(2-Fluorophenyl)-n-methoxy-n,2-dimethylacrylamide

Temperature

2.5 °C

N,O-dimethylhydroxylamine hydrochloride (7 g, 72 mmol) was slurried in CH2Cl2 (250 mL) and cooled to 0-5° C. A solution of trimethylaluminum (2M in toluene, 36 mL, 72 mmol) was added dropwise. The mixture was warmed to ambient temperature and stirred for 1 hr. A solution of Example 3A (5 g, 24.0 mmol) in CH2Cl2 (100 ml) was added and the solution was heated to reflux overnight. The reaction mixture was cooled in an ice bath and quenched carefully with ice cold 0.5 M HCl. The mixture was filtered through celite filter aid and extracted with CH2Cl2. The organic phase was washed with water and brine, dried over Na2SO4, filtered, and evaporated in vacuo. The crude product was chromatographed (SiO2, 100% hexanes to 20% ethyl acetate/hexanes) to afford the title compound (1.88 g, 35% yield) as a light yellow oil. 1H NMR (300 MHz, CDCl3) δ ppm 7.27-7.38 (m, 2H), 7.04-7.17 (m, 2H), 6.79 (s, 1H), 3.72 (s, 3H), 3.30 (s, 3H), 2.04 (s, 3H). MS (ESI+) 224 (M+H).

1. temperatureThe mixture was warmed to ambient temperature
2. temperaturethe solution was heated
3. temperatureto reflux overnight
4. temperatureThe reaction mixture was cooled in an ice bath
5. customquenched carefully with ice cold 0.5 M HCl
6. filtrationThe mixture was filtered through celite
7. filtrationfilter aid
8. extractionextracted with CH2Cl2
9. washThe organic phase was washed with water and brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. customevaporated in vacuo
13. customThe crude product was chromatographed (SiO2, 100% hexanes to 20% ethyl acetate/hexanes)

ORD record

ord-9b8243afbdc64537a81d379edb2f6046

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09108905B2