Carbon Dioxide → 5-chloro-6-fluoro-1H-indole-7-carboxylic acid

温度

10 °C

35 ml THF was cooled down to −75° C. under argon and 19.05 ml of a 1.6M solution of n-BuLi in hexane (30.5 mmol) were added. Then a solution of 2.35 g of 5-chloro-6-fluoro-1H-indole (13.7 mmol) in 9 ml THF was added dropwise (temperature kept between −70 and −75° C.) over 15 min. After 5 additional min stirring at this temperature a solution of 3.7 g potassium tert-butylate in 15 ml THF was added over 10 min (temperature kept between −70 and −75° C.). The brown solution was stirred 2 h at the same temperature and then treated with a large excess of solid CO2. The temperature was then raised to 10° C. over a period of 75 min, and treated with 30 ml water. After separation of the organic phase, the aqueous phase was extracted with 2×20 ml diethylether, treated with concentrated HCl until pH 1. The suspension was then filtered, the solid washed with water and dried in high vacuo. The residue was stirred with 10 ml hexane/diethylether 9:1 for 15 min and filtered, washed with 5 ml of the same mixture and the collected solid dried in high vacuo, leading to 2.2 g of 5-chloro-6-fluoro-1H-indole-7-carboxylic acid as a light brown solid (75%). MS: 212.2 (M−H)−.

1. additionwas added over 10 min (temperature kept between −70 and −75° C.)
2. customAfter separation of the organic phase
3. extractionthe aqueous phase was extracted with 2×20 ml diethylether
4. additiontreated with concentrated HCl until pH 1
5. filtrationThe suspension was then filtered
6. washthe solid washed with water
7. customdried in high vacuo
8. stirringThe residue was stirred with 10 ml hexane/diethylether 9:1 for 15 min
9. filtrationfiltered
10. washwashed with 5 ml of the same mixture
11. customthe collected solid dried in high vacuo

ORDレコード

ord-388fcf3a043b4d23884f259d1bb7d1f4

出典データセット

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07259183B2