2-(7-Fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid → 2-(5-Bromo-7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid

Temperature

0 °C

To a solution of 2.20 g of the acid from Step 2 (>90% purity) in 30 mL of pyridine, 6.85 g of pyridinium tribromide (90% purity) was added at −40° C. The suspension was stirred for 10 min at 0° C. and warmed to room temperature for 30 min. Then, the solvent was removed without heating under high vacuum. The crude material was dissolved in 40 mL of AcOH and 2.88 g of Zn dust was added portion wise to the cold solution at 0° C. The suspension was stirred for 15 min at 15° C. and warmed to room temperature for an additional 15 min. At this time, the reaction mixture was quenched by the addition of 1N HCl and this mixture was poured into a separatory funnel containing brine/EtOAc. The layers were separated and the organic layer was washed with water, brine, dried over anhydrous Na2SO4 and concentrated. This material was used without further purification in the next step.

1. temperaturewarmed to room temperature for 30 min
2. customThen, the solvent was removed
3. temperaturewithout heating under high vacuum
4. dissolutionThe crude material was dissolved in 40 mL of AcOH
5. addition2.88 g of Zn dust was added portion wise to the cold solution at 0° C
6. stirringThe suspension was stirred for 15 min at 15° C.
7. temperaturewarmed to room temperature for an additional 15 min
8. customAt this time, the reaction mixture was quenched by the addition of 1N HCl
9. additionthis mixture was poured into a separatory funnel
10. additioncontaining brine/EtOAc
11. customThe layers were separated
12. washthe organic layer was washed with water, brine
13. dry with materialdried over anhydrous Na2SO4
14. concentrationconcentrated
15. customThis material was used without further purification in the next step

ORD record

ord-b6505761f57641a18091a4dd8aeb8f0e

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07618994B2