Isobutanol → HCID 23434501, compound

Participants

Reaction Steps

A sodium hydride dispersion in mineral oil, 160.0 grams (60%, 4.0 moles) was placed in a 12 L round bottom flask equipped with mechanical stirrer, thermometer, addition funnel and nitrogen inlet. The flask was cooled with an ice bath and 3.5 L of dry THF added with sting, while maintaining the temperature below 20° C. To the suspension of stirred sodium hydride was added 376.4 grams (4.0 moles) of iso-butanol dissolved in 0.3 L of THF. The addition was carried out over about 2 hrs. at such a rate so as to maintain the temperature below 10° C. The mixture was then allowed to warm to room temperature and stired for 1 hour. To the re-cooled solution, over the course of 1 hour, was added 418 grams (2.0 moles) of ethyl 4-bromoacetoacetate (A. Svendsen, and P. M. Boll, Tetrahedron 1973 29, 4251-4258) dissolved in 0.3 L of THF. The rate of addition was controlled so as to keep the temperature below 10° C. The ice bath was removed and the brown slurry stirred overnight at room temperature. The reaction was quenched by pouring into 2.2 L of 1.0 N hydrochloric acid and the phases separated. The aqueous phase was extracted with 0.5 L of diethyl ether; the combined organic phase washed with 1.0 L of saturated brine and dried over MgSO4. After filtering and removal of solvent 830 g of a red-brown oil was obtained. The product was dissolved in 0.4 L of hexane and applied to a column of 8.0 L of silica wet-packed in hexane. The column was eluted with 4.0 L of hexane; 8.0 L of 3:1 hexane to diethyl ether and 12.0 L of 2:1 hexane to diethyl ether. The second fraction, 459.3 gram, was reapplied to a column of 4.0 L of silica wet-packed in hexane. The column was eluted with 3.0 L of 95:5 hexane to diethyl ether; 2.0 L of 9:1 hexane to diethyl ether; 2.0 L of 4:1 hexane to diethyl ether and 12.0 L of 3:1 hexane to diethyl ether. The major fraction was bulb-to-bulb distilled using a Kugelrohr apparatus and an oven temperature of 40-45° C. at <1.0 torr. The desired product was obtained as an oil, 145.9 gram (33%).

Provenance & Evidence