Hydrochloric Acid → HCID 17981723, compound

Temperature

-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-iodo benzimidazole (125 g, 342 mmol) and THF (1.2 L) and cool to −77° C. (results in a slurry). To this slurry add PhLi (1.8 M in c-hexane/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 t-BuLi (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 HCl(aq) and water (400 mL) until pH 2 is reached. Stir the mixture for 1 hour then adjust to pH>12 with 5 N NaOH while keeping the temperature <10° C. Add water (1 L), and separate the layers. Wash the aqueous layer with EtOAc (300 mL) then adjust to pH 6 with concentrated HCl(aq). Extract the mixture with EtOAc (2×700 mL), and dry the combined extracts (Na2SO4), 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 EtOAc (300 mL)
15. extractionExtract the mixture with EtOAc (2×700 mL)
16. dry with materialdry the combined extracts (Na2SO4)
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 record

ord-f5de2cb4aef9433284aad04c197f7309

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07320995B2