反应详情

温度

3 °C

A mixture of 729 ml of dry tetrahydrofuran and 76.4 ml of dry diisopropylamine was cooled to 3° C. with an ice-water bath. Then 340.6 ml of n-butyllithium in hexane was added dropwise over 45 minutes, followed by an additional 15 minutes of stirring. The solution was then cooled to -75° C. and 26.9 g of acetaldehyde t-butylimine was added dropwise with a syringe over 20 minutes, followed by an additional 30 minutes of stirring. With the temperature still at -75° C., 47.0 g of diethyl chlorophosphate was added with a dropping funnel over 1 hour. The reaction was allowed to stir for an additional hour at -75° C., warmed to -11° C. over 2 hours and cooled again to -75° C. Then, 28.4 g of methyl 4-oxocyclohexanecarboxylate in 50 ml of tetrahydrofuran was added with a dropping funnel over 1 hour. The reaction was allowed to warm to room temperature overnight. It was then poured into a mixture of 49.0 g of oxalic acid in 1.8 1 of water and 1.8 1 of toluene. This was stirred vigorously for 24 hours and the aqueous layer was then separated and extracted with ether (2×500 ml). The combined toluene and ether extracts were washed with aqueous 5% oxalic acid (2×500 ml), 500 ml of saturated sodium bicarbonate and 500 ml of saturated sodium chloride. The organic layer was then dried over anhydrous potassium carbonate, filtered and concentrated under vacuum. The resulting oil was purified on the Prep LC (25% ethyl acetate/hexane, 300 ml/min., 2 min./cm, 2 columns, Rt =7.5 min.) to give 18.5 g of methyl 4-(oxoethylidene)cyclohexanecarboxylate. 1H NMR (CDCl3, 60 MHz) δ 10.05 (d, 1 H); 5.85 (d, 1 H); 3.70 (s, 3 H); 2.8-1.5 (9 H).

1. temperatureThe solution was then cooled to -75° C.
2. waitfollowed by an additional 30 minutes
3. stirringof stirring
4. stirringto stir for an additional hour at -75° C.
5. temperaturewarmed to -11° C. over 2 hours
6. temperaturecooled again to -75° C
7. temperatureto warm to room temperature overnight
8. stirringThis was stirred vigorously for 24 hours
9. customthe aqueous layer was then separated
10. extractionextracted with ether (2×500 ml)
11. washThe combined toluene and ether extracts were washed with aqueous 5% oxalic acid (2×500 ml), 500 ml of saturated sodium bicarbonate and 500 ml of saturated sodium chloride
12. dry with materialThe organic layer was then dried over anhydrous potassium carbonate
13. filtrationfiltered
14. concentrationconcentrated under vacuum
15. customThe resulting oil was purified on the Prep LC (25% ethyl acetate/hexane, 300 ml/min., 2 min./cm, 2 columns, Rt =7.5 min.)