Dimethoxy-2-butyne

In 400 ml of anhydrous liquid ammonia (note 1) (drawn from a cylinder) in the 3-1 flask were dissolved 25 g of K0-tert.-Ci,tig (see Exp. 4, note 2). 1,4-Dimethoxy--2-butyne (Chapter VIII-6, Exp. 8) (0.60 mol) was poured into the solution. The reaction mixture was allowed to stand (with occasional swirling) for 25 min, after which 50 g of powdered ammonium chloride were introduced in 5 min with manual swirling. The ammonia was driven off by placing the flask in a water bath at 40 C. 

In order to synthesize the C5 acetate, dimethoxyacetone obtained by oxidation of acetone is ethynylated to 4,4-dimethoxy-3-methyl-l-butyn-3-ol in the presence of sodium hydroxide. Partial catalytic hydrogenation of the alkynol leads to 4,4-di-methoxy-3-methyl-l-buten-3-ol as the C5 alcohol which rearranges in acetie anhydride to the C5 aeetal ester. Deprotection of the aldehyde funetion necessary before the WiTTIG alkenylation is achieved thermally in the presence of copper(II)-salt as catalyst. 

A second route involved the intermediacy of benzophenone 351. Treatment of 3,5-dimefhoxyphenol (354) with 3-chloro-3-methyl-l-butyne (278) gave 5,7-dimethoxy-2,2-dimethylcln omene (359), which could be regioselectively lithiated at the 6-position by use of butyllithium in ether. Reaction of the lithio derivative 360 with 2-methyl-3,l-benzoxazin-4-one (255) smoothly afforded the required aminobenzophenone 351. Cyclization with sodium hydride in dimethylsulfoxide occurred with simultaneous loss of the acetyl group, to give 12-... 

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