反应详情

An oven-dried 3L 3-neck flask equipped with a mechanical stirrer, nitrogen inlet, nitrogen outlet and placed in a room-temperature water bath. After purging with nitrogen for 20 minutes, a solution of 1-propynylmagnesium bromide in THF (0.5 N, 600 mL) was added by cannula. In a separate oven-dried and nitrogen-flushed 500 mL RB flask, compound 1.1 (35 g, 142 mmol) was dissolved in anhydrous THF (350 mL) with gentle warming. The solution of 1.1 was then added over 15 minutes. Over the course of the addition, the reaction mixture changed to a thick, yellow suspension. After the addition was complete, the reaction mixture was stirred for 15 minutes and then quenched with aqueous NH4Cl (0.6N, 750 mL) and diluted with hexanes (800 mL). The layers were separated and the organic layer discarded. The aqueous layer was acidified to pH ˜2 with saturated aqueous KHSO4 and extracted with ethyl acetate (2×400 mL). The combined extracts were washed with saturated brine, dried over MgSO4, filtered, and concentrated to a light yellow solid (37 g, 91%). 1H NMR(500 MHz)(acetone-d6) δ 8.26 (s, 1H); 7.39 (d, 2H, J=8.5 Hz); 6.76 (d, 2H, J=8.4 Hz); 4.73 (br s, 1H); 4.46 (d, 1H, J=2.4 Hz); 1.82 (s, 3H); 1.81 (s, 3H); 1.64 (s, 3H). MS ESI (pos.) m/e: 599.0 (2M+Na).

1. dry with materialAn oven-dried 3L 3-neck flask
2. customequipped with a mechanical stirrer, nitrogen inlet, nitrogen outlet
3. customplaced in a room-temperature water bath
4. customAfter purging with nitrogen for 20 minutes
5. additiona solution of 1-propynylmagnesium bromide in THF (0.5 N, 600 mL) was added by cannula
6. customIn a separate oven-dried
7. customnitrogen-flushed 500 mL RB flask
8. additionThe solution of 1.1 was then added over 15 minutes
9. additionOver the course of the addition
10. additionAfter the addition
11. customquenched with aqueous NH4Cl (0.6N, 750 mL)
12. additiondiluted with hexanes (800 mL)
13. customThe layers were separated
14. extractionextracted with ethyl acetate (2×400 mL)
15. washThe combined extracts were washed with saturated brine
16. dry with materialdried over MgSO4
17. filtrationfiltered
18. concentrationconcentrated to a light yellow solid (37 g, 91%)