Water → HCID 22394611、化合物

To a solution of 1,4-dimethyl-1H-indole, (200 mg, 1.38 mmol) in tert-butanol (8 mL) was added water (4 mL) and the mixture was put at 50° C. In a separate flask was added potassium bromide (1.6 g, 13.8 mmol) followed by water (11 mL) and bromine (0.36 mL, 6.9 mmol). Next the bromine solution (8 was added dropwise to the 1,4-dimethyl-1H-indole mixture. After the addition was complete the temperature of the reaction was elevated to 70° C. for 30 min. The reaction was cooled to room temperature and diluted with dichloromethane and saturated aqueous sodium bicarbonate. The solution was then further diluted with saturated aqueous sodium thiosulfate. The layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting solid was filtrated with diethyl ether and one half of the solid, by weight, was then dissolved in acetic acid (2.5 Zinc dust (62 mg, 0.94 mmol) was then added. After 10 minutes the reaction mixture was filtered through a pad of Celite® and diluted with dichloromethane. The resulting solution was cooled to 0° C. and neutralized via the cautious addition of 2 N aqueous sodium hydroxide and saturated aqueous sodium bicarbonate. The resulting layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane 15 to 80%) to afford 5-bromo-1,4-dimethyl-1,3-dihydro-indol-2-one; 1H NMR (400 MHz, CDCl3) δ ppm 2.32 (s, 3H), 3.19 (s, 3H), 3.47 (s, 2H), 6.56 (d, J=8.1 Hz, 1H), 7.48 (d, J=8.1 Hz, 1H).

1. customwas put at 50° C
2. additionAfter the addition
3. customThe layers were separated
4. extractionthe aqueous layer was extracted two additional times with dichloromethane
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. filtrationThe resulting solid was filtrated with diethyl ether and one half of the solid, by weight
9. additionwas then added
10. filtrationAfter 10 minutes the reaction mixture was filtered through a pad of Celite®
11. additiondiluted with dichloromethane
12. temperatureThe resulting solution was cooled to 0° C. and neutralized via the cautious addition of 2 N aqueous sodium hydroxide and saturated aqueous sodium bicarbonate
13. customThe resulting layers were separated
14. extractionthe aqueous layer was extracted two additional times with dichloromethane
15. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated
18. customThe resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane 15 to 80%)

ORDレコード

ord-a00c5a4b34094070a4a53dba0b08aa03

出典データセット

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08778972B2