反应详情

温度

0 °C

A 50% oil dispersion of sodium hydride (0.38 g; 7.9 mmol) was washed three times with petroleum ether under a nitrogen atmosphere. The oil-free sodium hydride was suspended in 15 mol anhydrous tetrahydrofuran in a reaction vessel cooled in an ice bath. Then, with the sodium hydride suspension at 0° C. and stirred, there was added dropwise 25 ml anhydrous tetrahydrofuran containing 2.0 g (7.15 mmol) of ethyl 2-[(1,1-dimethylethyl)amino]-4-trifluoromethyl-5-oxazolecarboxylate (as prepared in Example 6. The reaction mixture was stirred for 1/2 hour at 0° C. and then 15 ml of anhydrous tetrahydrofuran containing 2.54 g (20 mmol) of methyl iodide was added dropwise to the mixture. The reaction mixture was stirred at room temperature for 3 hours. An additional 0.2 g (4 mmol) of 50% oil dispersion of sodium hydride (washed as before) was added and the mixture was stirred at room temperature for one hour. The reaction mixture was heated at reflux for 45 minutes, then stirred overnight at ambient temperature. The mixture was partitioned between ethyl ether and 5% hydrochloric acid solution. The organic phase was dried with sodium sulfate and concentrated under reduced pressure to yield 2.1 g of a reddish-brown product which was subjected to Kugelrohr distillation (100°-120° C. @ 2.5 mm Hg) to yield 1.7 g of a brown oil. This brown oil was dissolved in methylene chloride, washed with 10% sodium bisulfite, and concentrated under reduced pressure to yield 1.3 g of a colorless oil which was subjected to Kugelrohr distillation (100° C. @ 4 mm Hg) to yield 1.25 g of a pale yellow oil identified in Table I.

1. temperaturecooled in an ice bath
2. customas prepared in Example 6
3. stirringThe reaction mixture was stirred at room temperature for 3 hours
4. stirringthe mixture was stirred at room temperature for one hour
5. temperatureThe reaction mixture was heated
6. temperatureat reflux for 45 minutes
7. stirringstirred overnight at ambient temperature
8. customThe mixture was partitioned between ethyl ether and 5% hydrochloric acid solution
9. dry with materialThe organic phase was dried with sodium sulfate
10. concentrationconcentrated under reduced pressure