反应详情

温度

-70 °C

A 1.0 M solution of lithium hexamethyldisilazide in THF (310 mmol, 310 mL) was diluted with 20 mL of THF and cooled to -70° C. (internal temperature) with an acetone/dry ice bath under N2. A solution of 4'-methylacetophenone (150 mmol, 20.1 g, 20 mL) in 50 mL of tetrahydrofuran (THF) was added dropwise over a 15 min period, keeping the internal temperature below -60° C. After 1 h, the cooling bath was removed and the temperature was allowed to rise to -25° C. The reaction flask was immersed in an ice/acetone bath and a solution of ethyl diethoxyacetate (160 mmol, 28 g, 28.6 mL) in 20 mL of THF was added dropwise; during the addition, the internal temperature was kept below 0° C. The brown-red solution was stirred for 24 h and was re-cooled to 0° C. Aqueous HCl (3N, 618 mmol, 206 mL) was added carefully (temperature kept below 20° C.) to bring the pH to 3-4. The layers were separated and the aqueous layer was extracted with 200 mL of ether. The combined organic layers were washed twice with brine, dried over Na2SO4, and concentrated to give 40.3 g (100%) Cpd. 46 as an orange oil; 1H NMR (CDCl3, 300 MHz) 1.30 (t, 6H, J=7), 2.42 (s, 3H), 3.5-3.8 (complex, 4H), 4.90 (s, 1H), 6.58 (s, 1H), 7.28 (d, 2H, J=8), 7.74 (d, 2H, J=8), 15.8 (broad s, 1H)

1. customthe internal temperature below -60° C
2. customthe cooling bath was removed
3. customto rise to -25° C
4. customThe reaction flask was immersed in an ice/acetone bath
5. additionduring the addition
6. customwas kept below 0° C
7. temperaturewas re-cooled to 0° C
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with 200 mL of ether
10. washThe combined organic layers were washed twice with brine
11. dry with materialdried over Na2SO4
12. concentrationconcentrated
13. customto give 40.3 g (100%) Cpd