Water → 1-(7-Amino-2,3-dihydro-1,4-benzodioxin-6-yl)-2-chloroethan-1-one

1,4-benzodioxan-6-amine, Formula VIII, (160 g, 1.06 mol) is dissolved in dichloromethane (DCM, 2.4 L) and cooled in an ice bath to less than 10° C. Boron trichloride gas (150 g, 1.27 mol, 1.2 eq) is added over 0.75 hour. The resulting brown slurry is then stirred overnight at room temperature. The slurry is then cooled in an ice bath to 10° C. and chloroacetonitrile (94 mL, 1.48 mol, 1.4 eq) is added in one portion. Gallium chloride (205 g, 1.16 mol, 1.1 eq) is dissolved in DCM (310 mL) and added to the reaction over 0.5 h. The resulting brown slurry is then heated at reflux overnight (13-24 h). The brown solution is then cooled to rt and poured into a stirred mixture of DCM (6.4 L)) and water (6.4 L). The mixture is stirred for 1.5 to 2 h to allow the solids to dissolve. The layers are then separated and the aqueous phase is extracted with DCM (2 L). The organic layers are combined and concentrated under vacuum (about 100 mm Hg) to about 320 mL. (Crystallization occurs during the concentration.) Heptane (640 mL) is added over 1 hour and the slurry stirred overnight at room temperature. The slurry is filtered, washing the cake with heptane (200 mL). The cake is then dried overnight at 40° C. under high vacuum (about 1 mm Hg) to give 206 g (86%) of 1-(7-amino-2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-chloro-ethanone as a yellow solid.

1. temperaturecooled in an ice bath to less than 10° C
2. temperatureThe slurry is then cooled in an ice bath to 10° C.
3. additionadded to the reaction over 0.5 h
4. temperatureThe resulting brown slurry is then heated
5. temperatureat reflux overnight (13-24 h)
6. temperatureThe brown solution is then cooled to rt
7. stirringThe mixture is stirred for 1.5 to 2 h
8. dissolutionto dissolve
9. customThe layers are then separated
10. extractionthe aqueous phase is extracted with DCM (2 L)
11. concentrationconcentrated under vacuum (about 100 mm Hg) to about 320 mL
12. custom(Crystallization
13. concentrationoccurs during the concentration
14. addition) Heptane (640 mL) is added over 1 hour
15. stirringthe slurry stirred overnight at room temperature
16. filtrationThe slurry is filtered
17. washwashing the cake with heptane (200 mL)
18. customThe cake is then dried overnight at 40° C. under high vacuum (about 1 mm Hg)

ORD-Eintrag

ord-b5a08cfb8ddc46b8a3705a80ea953ee6

Quelldatensatz

uspto-grants-2000_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06063923