Hydroxyamine hydrochloride → HCID 86724402, compound

Temperature

50 °C

(S)-2-((1-fluorobut-3-en-2-yl)oxy)-1-(2-fluorophenyl)ethanone (63.25 g, 279.59 mmol) was dissolved in anhydrous methanol (620 mL) and hydroxylamine hydrochloride (25.26 g, 363.47 mmol) and sodium acetate (34.40 g, 419.39 mmol) were added. The reaction mixture was heated to 50° C. for 90 min, then cooled to RT. It was then filtered through celite, washed with EtOAc (600 mL) and concentrated in vacuo. EtOAc (500 mL) was added to the crude product followed by water (600 mL). The two layers were separated and the aqueous layer was extracted with EtOAc (2×500 mL). The combined organic extracts were dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (10% to 50% EtOAc in hexanes) to afford the title compound as a clear oil. It exists as a mixture of geometric isomers (67.76 g, 100%). 1H-NMR (400 MHz, CDCl3) δ ppm 3.91-4.06 (m, 1H) 4.16-4.19 (m, 1H) 4.29 (d, J=5.56 Hz, 1H) 4.78 (d, J=0.76 Hz, 2H) 5.24-5.43 (m, 2H) 5.57-5.77 (m, 1H) 7.06-7.14 (m, 1H) 7.15-7.24 (m, 1H) 7.35-7.41 (m, 1H) 7.47 (td, J=7.45, 1.77 Hz, 1H) 9.24 (br. s, 1H).

1. temperaturecooled to RT
2. filtrationIt was then filtered through celite
3. washwashed with EtOAc (600 mL)
4. concentrationconcentrated in vacuo
5. additionEtOAc (500 mL) was added to the crude product
6. customThe two layers were separated
7. extractionthe aqueous layer was extracted with EtOAc (2×500 mL)
8. dry with materialThe combined organic extracts were dried over MgSO4
9. concentrationconcentrated
10. customThe crude product was purified by silica gel chromatography (10% to 50% EtOAc in hexanes)

ORD record

ord-59a9e1205b07469da4455ae9f25f0a7f

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09175013B2