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To a solution of 8.2 g (0.046 mol) of III-24, 2.8 g of dry CjHsN, and 80 ml of dry PhMe, at -10°, was added dropwise 47 ml of a 15% w/v of COCli in PhMe. The work-up of this reaction mixture and the subsequent reaction of the intermediate carbamoyl chloride with EtOH-NIL followed the published procedure.Zc The yield of crude III-27 was 1.45 g; chromatography, in CeHe solution, on 60 g of alumina (Harshaw, Chromatographic Grade), followed by successive elutions with C«H6 and (-PrOH, and repeated recrystallizations from ß 6 were required to give pure III-28.8 5-Acetyl-7-chloro-5,ll-dihydrodibenz[b,e] [l,4]oxazepine (III-10).-A solution of 2.0 g (0.0087 mole) of 7-chloro-5,1 l-dihydro-' urm, < l at. dibenz]f),<:j [ 1,4] oxazepine,2* 25 ml of Ae-O, and 0.4 g of p-toluenesulfonic acid was heated under reflux for 2 hr, coned to dryness, and the residue distributed between 50 ml of Et»<) and 25 ml of said aq NaHCO». The Et»0 layer was sepd, washed with said a<[ NaCl, dried, and coned to give 2.4 g of 111-1(1.6-[ (o-Bromobenzy 1 )oxy] -Qf,a,a-trifluoro-»i-acetotoluidide . A mixture of 20.0 g (0.052 mol) of II-2. 8.6 g (0.1 1 mol) of anhyd AcONa, and 120 ml of glacial AeOH was heated under reflux for 3 hr, cooled somewhat, and poured into 300 ml of HiO. The oil, that sepd initially, solidified, and was filtered and dried to give 10.4 g of II-4.(8) The difficulties encountered in this synthesis are similar to those previously described in the oxazepine series, and are involved in the reaction of tiie heterocycle with phosgene."c Synthesis and Hypocholesterolemic Activity of Alkylidenedithio Bisphenols .

Probucol was effective in lowering serum total cholesterol in mice at dietary livels as low as 0.0075%. It was also effective after a single 100 mg/kg I.V. dose in mice. The incorporation of acetate-(14)C into liver lipids of rats and mice was not significantly affected by probucol, although the results, especially in mice, make it impossible to rule out such an effect. Cholesterol absorption was estimated in rats using a dual isotope technique. The observed reductions were not statistically significant. Several liver enzyme activities were determined after probucol treatment in rats, and a significant elevation (32%) was observed in only one, glutamic dehydrogenase. Serum cholesterol was lowered markedly in cholesterol-fed cynomolgus monkeys by probucol. There was no effect on the excretion of neutral steroids and the observed increase in fecal bile acids after drug treatment could not be confirmed statistically.