Dimethyl fumarate preparation

The preparation of partially reduced derivatives in which the five-membered ring is reduced is less well documented. In a series of papers, Huisgen reported the 1,3-dipolar reactivity of isoquinolinium imide 41 in which loss of aromaticity occurs during cycloaddition <1998EJ0379, 1998EJ0387, 1998T9848>. Cycloaddition of this compound with dimethyl fumarate or maleate gives 42 and 43 as mixture of diastereoisomers (Scheme 15). 

Addition of freshly prepared MgBr2.0Et2 to the reaction gave universal improvements in yield of the products (59). Previously poor dipolarophiles now gave good to excellent yields, especially in the case of dimethyl fumarate which. 

The checkers prepared diethyl fumarate by the sulfuric acid-catalyzed esterification of fumaric acid.7 Diethyl fumarate obtained from Aldrich Chemical Company, Inc., contained dimethyl fumarate as a contaminant. 

Acetaminothiophene has been prepared by a Hofmann rearrangement of thiophene-3-carboxamide (equation 49), or by a Beckmann rearrangement of the 3-acetylthiophene oxime (Section 3.14.3.4). Dimethyl 4-amino-2,3-thiophenedicarboxylate was formed in excellent yield from the oxime of the 4-ketotetrahydrothiophene diester, which is readily available by addition of thioglycolate to dimethyl fumarate, followed by a Dieckmann cyclization (equation 50 Section 3.15.2.2.2). 

Acyclic dienamines are relatively unstable, but very reactive towards electron-poor dienophiles as describe in a review article (1984). A more recent example shows the preparation of sterically encumbered 1-amino-1,3-diene (125) and its, nevertheless, efficient and highly stereoselective [4 + 2] cycloaddition to dimethyl fumarate (Scheme 32). Elimination of pyrrolidine, by heating the non-iso-lated cycloadduct with acetic anhydride, afforded hexahydronaphth ene (126), a key intermediate for a synthesis of drimane-type sesquiterpenes. 

Photolysis of a-cyanostilbene oxides has been examined in cydoaddition reactions with the dipolarophile dimethyl fumarate. The stereochemistry of the tetra-hydrofuran adduct prepared from the ylides formed in the disrotatory electro-cyclic ring-opening predicted by Woodward and Hoffman points to cis-trans isomerization of the carbonyl-ylide, probably via conrotatory cyclization. 

Nitrile sulfides are well suited for the synthesis of isothiazoles incorporating the C=N-S unit via their 1,3-dipolar cycloaddition reactions with double or triple-bonded dipolarophiles. Benzonitrile sulfide 210 is readily prepared from decarboxylation of oxathiazolone 209 using microwave irradiation <05SC807>. Subsequent cycloadditions to dimethyl acetylene-dicarboxylate (DMAD) and dimethyl fumarate afford 211 and 212, respectively. In the case of ethyl propiolate, a 1 1 regioisomeric mixture of phenylisothiazoles 213 and 214 is obtained. 

The experimental procedure described here for the preparation of Ru(ti -methyl acrylate)(C0)4 is applicable to a variety of other olefins as manifested by the syntheses of Ru(Ti -olefin)(CO)4 complexes of, for example, dimethyl fumarate, dimethyl maleate, allyl acrylate, methyl vinyl ketone (3-butene-2-one), and acrylonitrile. ... 

Extrusion of sulfur dioxide from oxidized thiophene derivatives is an exceptional method to prepare cis-dienes as components for Diels-Alder reactions. An example of this approach utilizes the Diels-Alder reactivity of the furan ring in substituted 4//,6ff-thieno[3,4-c]furan-3,S-dioxides to react with a variety of dienophiles such as DMAD, dimethyl maleate and dimethyl fumarate which then lose SO2 to form another reactive diene (Eq. 17) <94H961>. A review of the preparation and use of 4i/,6f/-thieno[3,4-c]furan-S,5-dioxides as well as other heteroaromatic-fused 3-suIfolenes is report <94H1417>. The preparation of dihydrothienooxazole 80 requires the careful control of the reaction time and temperature as well as the reactants molar ratio <94JOC2241>. Specific control of the alkylation conditions for 81 (X = COCH3) allows for the preparation of either 1,4-disubstituted or 1,6-disubstituted 4, 6//-thieno[3,4-c]furan-S,S-dioxides. These molecules could be used as intermediates for the preparation of novel pentacyclic compounds <94JCS(P1)1371>. 

To investigate the effects of various substituents on the a-phosphono enecarbamate core structure, a variety of chloro- or methoxy-substituted substrates 361b-h were prepared and treated with Pd(PPh3)4, K2CO3, and dimethyl fumarate (335) in CH3CN at 70°C. In aU cases, the desired tetrahydrocarbazoles 364 were formed in good to excellent yields (Scheme 79). 

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