Hydrochloric Acid → 4,5-Dihydro-5-methyl-3,4-diphenyl-5-isoxazolol

温度

-20 °C

The deoxybenzoin oxime (Step 1) was dissolved in anhydrous THF (565 mL) under a nitrogen atmosphere. The solution was cooled to −20° C. The solution was treated with lithium diisopropylamide (2 M, 800 mL, 1.60 mol) while allowing the reaction temperature to warm to 10-15° C. The reaction mixture to was cooled to −10° C. to −20° C. and anhydrous ethyl acetate (218 mL) was added to the solution while allowing the reaction temperature to rise to a maximum of 25° C. and held for 30 minutes at 25° C. The reaction mixture was cooled to about 0° C. Water was added to a quench flask and cooled to 0-5° C. The pre-cooled reaction mixture was transferred from the reaction flask to the quench flask while maintaining the temperature of the quench mixture below 25° C. The quenched mixture was cooled to 0-5° C. Hydrochloric acid (12 M) was added to the mixture, keeping the temperature below 25° C. during the addition by controlling the addition rate and stirred until all the solids dissolve (˜5 minutes). The pH of the stirred mixture was measured to be pH 3-4. The layers were separated and the organic layer was removed. Heptane was added to the organic layer with stirring. The organic layer was distilled until the pot temperature reached 90-91° C. The solution was cooled to 5° C. and filtered. The solid was washed with two 300 mL portions of ethyl acetate-heptane (20/80), cooled to 5° C. The solid product was dried on the funnel for several hours then dried at ambient under vacuum with a nitrogen sweep over the weekend to yield the isoxazoline (108.75 g, 57.7%).

1. temperatureto warm to 10-15° C
2. temperatureThe reaction mixture to was cooled to −10° C. to −20° C.
3. customto rise to a maximum of 25° C.
4. temperatureThe reaction mixture was cooled to about 0° C
5. temperaturecooled to 0-5° C
6. customThe pre-cooled reaction mixture
7. temperaturewhile maintaining the temperature of the quench mixture below 25° C
8. temperatureThe quenched mixture was cooled to 0-5° C
9. customthe temperature below 25° C.
10. additionduring the addition
11. dissolutiondissolve (˜5 minutes)
12. customThe layers were separated
13. customthe organic layer was removed
14. additionHeptane was added to the organic layer
15. stirringwith stirring
16. distillationThe organic layer was distilled until the pot temperature
17. customreached 90-91° C
18. temperatureThe solution was cooled to 5° C.
19. filtrationfiltered
20. washThe solid was washed with two 300 mL portions of ethyl acetate-heptane (20/80)
21. temperaturecooled to 5° C
22. customThe solid product was dried on the funnel for several hours
23. customthen dried at ambient under vacuum with a nitrogen sweep over the weekend

ORDレコード

ord-28c46e85b1ba408c87d6168a974f8014

出典データセット

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07135489B2