3-Methyl-4-dimethylamino-butanone

A soln. of o)-diazoacetophenone in tetrahydrofuran added gradually at 0° to a stirred soln. of triethylborane in anhydrous tetrahydrofuran, stirred 1.5 hrs. at room temp, until Ng-evolution is complete, a soln. of the Mannidi reagent di-methyl(methylene)ammonium iodide in anhydrous dimethyl sulfoxide added with stirring, which is continued at room temp, up to 3 hrs., cooled to 0°, 3 iV NaOH-soln. added, and vigorously stirred for 15 min. l-phenyl-2-dimethylamino-methyl-l-butanone. Y 70-92%. F. e. s. J. Hooz and J. N. Bridson, Am. Soc. 95, 602 (1973). 

At this temperature 4-(dimethylamino)-3,3-dimethyl-2-butanone, which is formed initially, isomerizes to l-(dimethyl-amino)-4-methyl-3-pentanone. 

A. Isopvopylidensaaetophenone. A 1-L, three-necked flask is fitted with a 100-mL pressure-equalizing dropping funnel, a mechanical stirrer and a condenser which is equipped with a two-way stopcock leading to a balloon of argon gas. To the flask is added a solution of 18,4 g of 3-hydroxy-3-methyl-1-phenyl-1-butanone (Note 1) in 60 mL of dry methylene chloride. The flask is cooled 1n an ice bath and 28.5 g of trlethylamine, a catalytic amount of 4-(N,N-dimethylamino)pyridine and 20 mL of methylene chloride are added. A solution of 25.8 g of trlfluoroacetic anhydride (Note 2) in 40 mL of methylene chloride Is added dropwlse over a period of 15 min, and the mixture is stirred for 2. 5 hr. ... 

The synthesis of lupeol starts with the cyclization of 6-methoxy-p-methyl-a-tetralone 28 with 4-7V 7V -dimethylamino-2-butanone methiodide in the presence of potassium /-butanolate to l,9,10,10a-tetrahydro-7-methoxy-3(2//)-phenanthrone 27. Reduction with sodium borohydride and subsequent hydrogenation of the enone CC double bond in the presence of palladium and strontium carbonate as slightly deactivated catalyst gives the oetahydrophenanthrol 26. Partial reduction of the benzenoid ring to the enone is aceomplished by lithium in liquid ammonia. The enone is derivatized to the benzoate 25 in order to protect the hydroxy group prior to the subsequent synthetic steps. 

The initial version of the reaction (as illustrated by entry 1) used an in situ source of methyl vinyl ketone. The quaternary salt of 4-dimethylamino-2-butanone decomposes easily to the unsaturated ketone. In more recent procedures—for example, entries 2-4—the a,j8-unsaturated ketone is added directly. Entry 3 illustrates the use of the enamine of a ketone as the reactive nucleophile in a Robinson annelation. 

Dimethylamino)-1-(4-(4-morpholinyl) phenyl)-2-(phenylmethyl)-1-butanone. See 2-Benzyl-2-(dimethylamino)-4 -morpholinobutyrophenone 4-(Dimethylamino) nitrosobenzene p-(Dimethylamino) nitrosobenzene. See N,N-Dimethyl-p-nitrosoaniline 4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,6,10,12,12a-hexahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride. See Oxytetracycline hydrochloride... 

Methyl-2-morpholino(4-thiomethylphenyl)propane-l-one 2-Benzyl-2-dimethylamino-l-(4-morpholinophenyl)-l-butanone 2,4,6-Trimethylbenzoindiphenyl-phosphine oxide Methylphenyl glyoxyesters... 

---