Potassium Carbonate → HCID 22497221, compound

Temperature

60 °C

A mixture of 1-(6-chloro-1H-indol-3-yl)-2,2,2-trifluoro-ethanone (300 mg, 1.21 mmol), potassium carbonate (419 mg, 3.03 mmol), and (bromomethyl)-cyclobutane (0.21 mL, 1.82 mmol) in N,N-dimethylformamide (4 mL) in a sealed reaction vessel was heated at 60° C. for 16 h. At this time, the reaction was cooled to 25° C. and partitioned between water (30 mL) and ethyl acetate (30 mL). This mixture was treated with a 1N aqueous hydrochloric acid solution (6 mL), shaken, and separated. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a yellow solid. The resulting solid was treated with a 20% aqueous sodium hydroxide solution (7 mL) and was heated at 115° C. for 24 h. At this time, the reaction was cooled to 25° C. and was partitioned between water (75 mL) and ethyl acetate (75 mL). This solution was treated with a 1N aqueous hydrochloric acid solution (30 mL), shaken, and separated. The organic layer was washed with a saturated aqueous sodium chloride solution (1×50 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 6-chloro-1-cyclobutylmethyl-1H-indole-3-carboxylic acid (318 mg, 99%) as a yellow solid: mp 191-193° C.; EI-HRMS m/e calcd for C14H14ClNO2 (M+) 263.0713, found 263.0715.

1. customin a sealed reaction vessel
2. temperatureAt this time, the reaction was cooled to 25° C.
3. custompartitioned between water (30 mL) and ethyl acetate (30 mL)
4. additionThis mixture was treated with a 1N aqueous hydrochloric acid solution (6 mL)
5. customseparated
6. dry with materialThe organic layer was dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto afford a yellow solid
10. temperaturewas heated at 115° C. for 24 h
11. temperatureAt this time, the reaction was cooled to 25° C.
12. customwas partitioned between water (75 mL) and ethyl acetate (75 mL)
13. additionThis solution was treated with a 1N aqueous hydrochloric acid solution (30 mL)
14. stirringshaken
15. customseparated
16. washThe organic layer was washed with a saturated aqueous sodium chloride solution (1×50 mL)
17. dry with materialdried over magnesium sulfate
18. filtrationfiltered
19. concentrationconcentrated in vacuo

ORD record

ord-d4d3fe691074428fb97dac73c3b8831c

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881844B2