反应详情

To a stirred solution of 5-bromo-3-(1-methylethyl)-1H-indole-7-carboxylic acid (4.1 g, 14.53 mmol) in DMF (100 mL) at 0° C. was added iodomethane (3.6 mL, 57.6 mmol) followed by sodium hydride 60% dispersion in oil (1.4 g, 35.0 mmol) portionwise over 15 minutes. The reaction was allowed to warm to RT and stirred for 2 h. The reaction was recooled to 0° C., carefully quenched with water (5 mL), and evaporated to near dryness under vacuum. The residue was taken up in MeOH (50 mL) then treated with 6 N NaOH (10 mL, 60.0 mmol). The reaction was heated to 60° C. and stirred for 4 h. After cooling to RT the reaction was concentrated to near dryness, diluted with water, acidified with 6 N HCl (10 mL, 60 mmol), extracted with CH2Cl2, dried (Na2SO4), filtered, and evaporated to dryness to give the crude acid as a brown solid. Purification by silica gel chromatography (Analogix, SF40-120 g, 0 to 50% EtOAc in hexanes) gave material which was triturated with hexanes, filtered and dried under vacuum to give the product 5-bromo-1-methyl-3-(1-methylethyl)-1H-indole-7-carboxylic acid (2.98 g, 10.06 mmol, 69.2% yield) as a white solid. MS (ES)+ m/e 296.3 [M+H]+.

1. customwas recooled to 0° C.
2. customcarefully quenched with water (5 mL)
3. customevaporated
4. temperatureThe reaction was heated to 60° C.
5. stirringstirred for 4 h
6. temperatureAfter cooling to RT the reaction
7. concentrationwas concentrated
8. additiondiluted with water
9. extractionextracted with CH2Cl2
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. customevaporated to dryness
13. customto give the crude acid as a brown solid
14. customPurification by silica gel chromatography (Analogix
15. customSF40-120 g, 0 to 50% EtOAc in hexanes) gave material which
16. customwas triturated with hexanes
17. filtrationfiltered
18. customdried under vacuum