Hydrochloric Acid → HCID 17981723, Verbindung

Temperatur

-77 °C

Charge a 5 L round bottom flask equipped with dry ice/acetone bath, nitrogen atmosphere, mechanical stirrer, thermocouple, and addition funnel with septum with 1-isopropylsulfonyl-2-amino-6-iodobenzimidazole (125 g, 342 mmol) and tetrahydrofuran (1.2 L) and cool to −77° C. (results in a slurry). To this slurry add phenyllithium (1.8 M in cyclohexane/diethyl ether, 599 mL, 1078 mmol) over 25 minutes keeping the temperature below −67° C. After stirring the resulting green slurry for 20 minutes while cooling to −77° C., add tert-butyllithium (1.7 M in pentane, 503 mL, 856 mmol) over 25 minutes keeping the temperature of the reaction below −67° C. Stir the mixture at −75° C. for 40 minutes then add triisopropyl borate (276 mL, 1198 mmol) over 15 minutes keeping the temperature below −65° C. Warm the resulting slurry slowly to 0° C. over 2 hours, then add a mixture of concentrated hydrochloric acid and water (400 mL) until pH 2 is reached. Stir the mixture for 1 hour then adjust to pH>12 with 5 N sodium hydroxide while keeping the temperature <10° C. Add water (1 L), and separate the layers. Wash the aqueous layer with ethyl acetate (300 mL) then adjust to pH 6 with concentrated hydrochloric acid. Extract the mixture with ethyl acetate (2×700 mL), dry the combined extracts over sodium sulfate, filter, and concentrate in vacuo to an orange paste (116 g). Dissolve the paste in warm (˜60° C.) 2-propanol (360 mL) then add water (1.4 L). Cool the solution to 0° C. for 3 hours. Collect the resulting solid by filtration, wash with water then air-dry to constant weight to afford the title compound (34.9 g, 36% yield) as light tan crystals. Obtain a second crop from the filtrate (4.95 g, 41% yield overall). MS (ES+): m/z=284 (M+H)+

1. additionCharge a 5 L round bottom flask
2. customequipped with dry ice/acetone bath
3. customresults in a slurry)
4. customthe temperature below −67° C
5. temperaturewhile cooling to −77° C.
6. customthe temperature of the reaction below −67° C
7. stirringStir the mixture at −75° C. for 40 minutes
8. customthe temperature below −65° C
9. temperatureWarm the resulting slurry slowly to 0° C. over 2 hours
10. additionadd
11. stirringStir the mixture for 1 hour
12. customthe temperature <10° C
13. customAdd water (1 L), and separate the layers
14. washWash the aqueous layer with ethyl acetate (300 mL)
15. extractionExtract the mixture with ethyl acetate (2×700 mL)
16. dry with materialdry the combined extracts over sodium sulfate
17. filtrationfilter
18. concentrationconcentrate in vacuo to an orange paste (116 g)
19. dissolutionDissolve the paste
20. temperaturein warm (˜60° C.) 2-propanol (360 mL)
21. temperatureCool the solution to 0° C. for 3 hours
22. customCollect the resulting solid
23. filtrationby filtration
24. washwash with water
25. customthen air-dry to constant weight

ORD-Eintrag

ord-4a6fd4d0238744b4a90b60fa90413df0

Quelldatensatz

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07863310B2