合成路线1

Delmopinol can be obtained by three different ways: 1) The reaction of 2-(benzylamino)-6-propylnonan-1-ol (I) with ethylene oxide (II) in ethanol at 100 C yields the corresponding N-(2-hydroxyethyl)derivative (III), which is cyclized with H2SO4 at 140-150 C to 4-benzyl-3-(4-propylheptyl)morpholine (IV). The debenzylation of (IV) by hydrogenolysis with H2 over Pd/C affords the free morpholine (V), which is finally condensed with 2-chloroethanol (VI) by means of KI and KOH in refluxing ethanol. 2) The Grignard condensation of 4-heptanone (VII) with allyl bromide (VIII) in ethyl ether gives 4-propyl-1-hepten-4-ol (IX), which is cyclocondensed with morpholine (X) by means of H2O2 and Na2WO4 in methanol to yield 4-(perhydroisoxazol[3,2-c][1,4]oxazin-2-ylmethyl)-4-heptanol (XI). Reductive ring opening of (XI) by hydrogenation with H2 over Pd/C and p-toluenesulfonic acid in isopropanol affords a mixture of the morpholine (V) and the hydroxymorpholine (XII). This mixture, without separation, is treated first with SOCl2 in chloroform to perform Cl-OH interchange, then with NaOH to obtain the corresponding double bond, and finally, the mixture is hydrogenated with H2 over Ra-nickel and triethylamine in dioxane in order to obtain pure (V), already obtained. 3) The acylation of the alkylmorpholine (V) with oxalic acid monomethyl ester (XIII) by means of triethylamine in refluxing benzene gives the corresponding condensation compound (XIV), which is then reduced with LiAlH4 in refluxing ethyl ester.