反应详情

To a mixture of 5 g (30.4 mmol) of 5-(2,2-dimethyl-propyl)-isoxazole-3-carbonitrile and 10.1 ml (34.1 mmol) of titanium(IV) isopropoxide in 150 ml of dry diethyl ether a solution of 22 ml of ethylmagnesium bromide (3 M in diethyl ether, 66.0 mmol) is added at −70° C. The reaction mixture is allowed to reach rt within two hours, 7.6 ml (60.6 mmol) of boron trifluoride-diethyl etherate are added and stirring is continued for one hour. After addition of 90 ml of 1M aq hydrochloric acid and 450 ml of diethyl ether two clear phases are obtained which are treated with 300 ml of 10% aq sodium hydroxide. The aqueous phase is extracted with diethyl ether, the combined organic phases are dried over sodium sulfate and evaporated to afford a dark orange oil. After filtration over a C18-bond elut column (Varian) with THF/MeCN the oil is purified by HPLC (dissolved in 6 ml of tetrahydrofuran, 25 injections, XBridge C18 column, 19×150 mm, 5 μM, gradient of 95% MeCN in water to 10% MeCN in water, containing 0.02% of ammonium hydroxide). The combined product fractions are concentrated and the product is extracted with DCM to yield the product as an orange solid.

1. additionis added at −70° C
2. waitis continued for one hour
3. customare obtained which
4. extractionThe aqueous phase is extracted with diethyl ether
5. dry with materialthe combined organic phases are dried over sodium sulfate
6. customevaporated
7. customto afford a dark orange oil
8. filtrationAfter filtration over a C18-bond elut column (Varian) with THF/MeCN the oil
9. customis purified by HPLC (dissolved in 6 ml of tetrahydrofuran, 25 injections, XBridge C18 column, 19×150 mm, 5 μM, gradient of 95% MeCN in water to 10% MeCN in water, containing 0.02% of ammonium hydroxide)
10. concentrationThe combined product fractions are concentrated
11. extractionthe product is extracted with DCM