Sectral ,May and Baker ,UK ,1975
Crude 5'-butyramido-2'-(2,3-epoxypropoxy)acetophenone (16 g),
isopropylamine (20 g) and ethanol (100 ml) were heated together under
reflux for 4 hours. The reaction mixture was concentrated under reduced
pressure and the residual oil was dissolved in N hydrochloric acid. The acid
solution was extracted with ethyl acetate, the ethyl acetate layers being
discarded. The acidic solution was brought to pH 11 with 2 N aqueous sodium
hydroxide solution and then extracted with chloroform. The dried chloroform
extracts were concentrated under reduced pressure to give an oil which was
crystallized from a mixture of ethanol and diethyl ether to give 5'-butyramido-
2'-(2-hydroxy-3-isopropylaminopropoxy)acetophenone (3 g), MP 119-123°C.
Crude 5'-butyramido-2'-(2,3-epoxypropoxy)acetophenone used as starting
material was prepared as follows: p-butyramidophenol (58 g; prepared
according to Fierz-David and Kuster, Helv. Chim. Acta 1939,2282), acetyl
chloride (25.4 g) and benzene (500 ml) were heated together under reflux
until a solution formed (12 hours). This solution was cooled and treated with
water. The benzene layer was separated and the aqueous layer was again
extracted with benzene.
The combined benzene extracts were dried and evaporated to dryness under
reduced pressure to give p-butyramidophenyl acetate (38 g) as an off-white
solid, MP 102-103°C. A mixture of p-butyramidophenyl acetate (38 g),
aluminum chloride (80 g) and 1,1,2,2-tetrachloroethane (250 ml) was heated
at 140°C for 3 hours. The reaction mixture was cooled and treated with iced
water. The tetrachloroethane layer was separated and the aqueous layer was
extracted with chloroform. The combined organic layers were extracted with 2
N aqueous sodium hydroxide and the alkaline solution was acidified to pH 5
with concentrated hydrochloric acid. The acidified solution was extracted with
chloroform and the chloroform extract was dried and concentrated under
reduced pressure to give 5'-butyramido-2'-hydroxyacetophenone (15.6 g), MP
114-117°C. A solution of 5'-butyramido-2'-hydroxyacetophenone (15.6 g) in ethanol (100 ml) was added to an ethanolic solution of sodium ethoxide which
was prepared from sodium (1.62 g) and ethanol (100 ml). The resulting
solution was evaporated to dryness under reduced pressure and
dimethylformamide (100 ml) was added to the solid residue. Approximately
10 ml of dimethylformamide was removed by distillation under reduced
pressure. Epichlorohydrin (25 ml) was added and the solution was heated at
100°C for 4 hours. The solution was concentrated under reduced pressure to
give a residual oil which was treated with water to give a solid. The solid was
dissolved in ethanol and the resulting solution was treated with charcoal,
filtered and concentrated under reduced pressure to give crude 5'-butyramido-
2'-(2,3-epoxypropoxy)acetophenone (16 g), MP 110-116°C.
The crude compound may be purified by recrystallization from ethyl acetate,
after treatment with decolorizing charcoal, to give pure 5'-butyramido-2'-(2,3-
epoxypropoxy)acetophenone, MP 136-138°C.
Poison by ingestion, subcutaneous,intravenous, and intraperitoneal routes. An experimentalteratogen. Other experimental reproductive effects. Whenheated to decomposition it emits toxic fumes of NOx andHCl.
