反应详情

温度

-70 °C

Dissolve 6-bromo-4-methyl-quinoline (38.5 g, 153 mmol) in 600 mL dry THF. Cool to −70° C. and treat with the dropwise addition of 0.5 M potassium hexamethyldisilazane (KN(SiMe3)2 (400 mL, 200 mmol) over 2 hours while keeping the temperature below −65° C. Stir the resultant solution at −70° C. for 1 hour and add a solution of 6-methylpyridine-2-carboxylic acid methyl ester (27.2, 180 mmol) in 100 mL dry THF dropwise over 15 minutes. During the addition, the mixture will turn from dark red to pea-green and form a precipitate. Stir the mixture at −70° C. over 2 hours then allow it to warm to ambient temperature with stirring for 5 hours. Cool the mixture then quench with 12 N HCl to pH=1. Raise the pH to 9 with solid potassium carbonate. Decant the solution from the solids and extract twice with 200 mL ethyl acetate. Combine the organic extracts, wash with water and dry over potassium carbonate. Stir the solids in 200 mL water and 200 mL ethyl acetate and treat with additional potassium carbonate. Separate the organic portion and dry with the previous ethyl acetate extracts. Concentrate the solution in vacuo to a dark oil. Pass the oil through a 300 mL silica plug with methylene chloride then ethyl acetate. Combine the appropriate fractions and concentrate in vacuo to yield an amber oil. Rinse the oil down the sides of the flask with methylene chloride then dilute with hexane while swirling the flask to yield 38.5 g (73.8%) of the desired subtitled intermediate as a yellow solid. MS ES+=341 (M+1).

1. customthe temperature below −65° C
2. additionDuring the addition
3. customform a precipitate
4. temperatureto warm to ambient temperature
5. stirringwith stirring for 5 hours
6. temperatureCool the mixture
7. customthen quench with 12 N HCl to pH=1
8. temperatureRaise the pH to 9 with solid potassium carbonate
9. customDecant the solution from the solids
10. extractionextract twice with 200 mL ethyl acetate
11. washwash with water
12. dry with materialdry over potassium carbonate
13. stirringStir the solids in 200 mL water
14. addition200 mL ethyl acetate and treat with additional potassium carbonate
15. customSeparate the organic portion
16. dry with materialdry with the previous ethyl acetate extracts
17. concentrationConcentrate the solution in vacuo to a dark oil
18. concentrationconcentrate in vacuo
19. customto yield an amber oil
20. washRinse the oil down the sides of the flask with methylene chloride
21. additionthen dilute with hexane