Iodoethane → HCID 58382052, compound

Temperature

-40 °C

The 4-chloro-3-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (27.0 g, 62.1 mmol) in THF (300 mL) was cooled to about −75° C. then t-BuLi (1.7 M in pentane, 73.1 mL, 124 mmol) was added over about 30 min keeping the internal temperature below about −70° C. After complete addition, EtI (15.0 mL, 186 mmol) was added. The mixture was warmed slowly to about −40° C. then the mixture was allowed to warm to rt. Saturated aqueous NaHCO3 (50 mL) was added and the mixture was stirred for about 30 min. The mixture was filtered and the solids washed with EtOAc (3×50 mL). The solvents were removed under reduced pressure then the material was partitioned between EtOAc (200 mL) and water (50 mL). The layers were separated then the organic layer was washed with saturated aqueous NaCl (50 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The resulting material was treated with MeOH (80 mL) then warmed to about 60° C. The mixture was cooled to rt and the resulting slurry stirred overnight at rt. The solids were collected by filtration then washed with MeOH (10 mL). The filtrate was concentrated under reduced pressure then purified by silica gel chromatography using a 120 g silica gel column and eluting with heptane. The material was stirred with MeOH (15 mL) overnight then the solid was collected by filtration and washed with MeOH (2 mL). The solid material was combined with the first crop of solids and dried under reduced pressure to give 4-chloro-3-ethyl-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (17.4 g, 83%): LC/MS (Table 2, Method g) Rt=3.21 min; MS m/z 337 (M+H)+.

1. customthe internal temperature below about −70° C
2. additionwas added
3. temperatureto warm to rt
4. filtrationThe mixture was filtered
5. washthe solids washed with EtOAc (3×50 mL)
6. customThe solvents were removed under reduced pressure
7. customthe material was partitioned between EtOAc (200 mL) and water (50 mL)
8. customThe layers were separated
9. washthe organic layer was washed with saturated aqueous NaCl (50 mL)
10. dry with materialdried over anhydrous MgSO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. additionThe resulting material was treated with MeOH (80 mL)
14. temperaturethen warmed to about 60° C
15. temperatureThe mixture was cooled to rt
16. stirringthe resulting slurry stirred overnight at rt
17. filtrationThe solids were collected by filtration
18. washthen washed with MeOH (10 mL)
19. concentrationThe filtrate was concentrated under reduced pressure
20. customthen purified by silica gel chromatography
21. washeluting with heptane
22. stirringThe material was stirred with MeOH (15 mL) overnight
23. filtrationthe solid was collected by filtration
24. washwashed with MeOH (2 mL)
25. customdried under reduced pressure

ORD record

ord-d674d419230d4648a4aca35399a7fc28

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785639B2