Hydrochloric Acid → 5-Bromo-3-[2-(4-methoxy-phenyl)-ethyl]-indole-1-carboxylic acid diethylamide

Temperature

-78 °C

To a solution of 4-methoxybenzyl triphenyphosphonium chloride (7.5 g, 18 mmol) in anhydrous THF (75 mL) at −78° C. was added LDA (9.0 mL, 18 mmol) and the resulting reaction mixture was allowed to stir at −78° C. for 1 h. Thereafter, 5-bromo-3-formyl-indole-1-carboxylic acid diethylamide (1.9 g, 6 mmol, Example 1, Part A) was added and the resulting reaction mixture was allowed to stir at −78° C. for 1 h and then warmed to room temperature to stir overnight. The reaction mixture was poured onto 1N HCl solution and extracted with ethyl acetate. The combined ethyl acetate extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by chromatography on silica gel eluting with ethyl acetate/hexane (1:4) to provide the mixture of alkenes (2.3 g, 90%, E:Z ˜1:1) as a brown oil. A solution of the above alkenes (2.3 g, 5.4 mmol) in dichloromethane (100 mL) was hydrogenated over Adam's catalyst (300 mg) under H2 (15 psi) for 2 h. The catalyst was removed by filtration and the filtrate was concentrated in vacuo. The crude product was purified by chromatography on silica gel eluting with ethyl acetate/hexane (1:4) to provide the title compound (1.43 g, 62%) as a colorless oil.

1. customthe resulting reaction mixture
2. customthe resulting reaction mixture
3. stirringto stir at −78° C. for 1 h
4. temperaturewarmed to room temperature
5. stirringto stir overnight
6. extractionextracted with ethyl acetate
7. washThe combined ethyl acetate extracts were washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated in vacuo
10. customThe crude product was purified by chromatography on silica gel eluting with ethyl acetate/hexane (1:4)
11. customto provide
12. customThe catalyst was removed by filtration
13. concentrationthe filtrate was concentrated in vacuo
14. customThe crude product was purified by chromatography on silica gel eluting with ethyl acetate/hexane (1:4)

ORD record

ord-9edeeb72ba5a488e8b3410b0e4f9bd70

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07482330B2