3-Furoate

Molecular formula CzTHaoClaOg Molecular weight 521.4 CAS Registry No. 83919-23-7 

Sample preparation Dissolve in MeCNrTHF 94.3 5.7, inject an aliquot. 

Mobile phase MeCNiTHF 15 mM pH 4.1 acetate buffer 41.5 2.5 56 Flow rate 2 Detector UV 254 

Simultaneous degradation products, impurities, benzaldehyde, benzyl alcohol, clotrimazole, orthochlorophenyl-diphenylmethanol 

Spangler, M. Isocratic reversed phase HPLC analysis of a pharmaceutical cream. Supelco Reporter, 1994, 13(2), 12-13 

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The Feist-Benary furan synthesis occurs when an a-halocarbonyl (1) reacts with a P-dicarbonyl (2) in the presence of a base. The resulting product (3) is a 3-furoate that incorporates substituents present in the two starting materials. ... 

In 1911 Benary reported a modification of Feist s original procedure. He reacted chloroacetaldehyde (8), generated in situ from the ammonia promoted decomposition of 1,2-dichloroethyl ethyl ether (7), with ethyl acetoacetate (9) and ammonia to yield ethyl 2-methyl 3-furoate (10). ... 

Syntheses of trisubstituted furans are much less common than the disubstituted derivatives only one 2,4-disubstituted 3-furoate has been prepared using the Feist-Benary reaction. Combination of chloroacetone (4) with ethyl acetoacetate (9) provides ethyl 2,4-dimethyl-3-furoate (28) in 54-57% yield. The procedure for this... 

Step reaction provides an excellent alternative to the traditional Feist-Benary protocol for the synthesis of 2-substituted 3-furoates. 

The final variation of the Feist-Benary furan synthesis encompasses reactions of 1,3-dicarbonyls with 1,2-dibromoethyl acetate (52). For example, treatment of ethyl acetoacetate (9) with sodium hydride followed by addition of 52 at 50°C yields dihydrofuran 53. The product can be easily converted into the corresponding 2-methyl-3-furoate upon acid catalyzed elimination of the acetate, thus providing another strategy for the synthesis of 2,3-disubstituted furans. 

Both 2,5-dialkyl-3-furoates and 2,5-dialkyl-3-phosphonofurans can be produced using the Paal-Knorr reaction. Methyl 2,5-diisopropyl-3-furoate (62) is available upon treatment of dione 61 with sulfuric acid. Phosphonodiones 63 can be efficiently converted into 2-substituted-3-diethylphosphono-5-methylfurans 64 by exposure to Amberlyst in refluxing toluene. ... 

Glycolaldehyde also reacts in dilute solution with ethyl acetoacetate, under conditions analogous to those for D-glycerose, to give ethyl 2-methyl-3-furoate.16 The corresponding acid was identified as 2-methyl-3-furoic acid (IV). 

Experimental Procedure 4.2.10. Cycloaddition of an Acylcarbene Complex to an Enol Ether Ethyl 5-Ethoxy-2-trifluoromethyl-4,5-dihydro-3-furoate [1417]... 

Supporting evidence for the presence of the equilibrium 101 102 is found in the work of Gomez Sanchez and Roldan,2093 who found that the dehydration of both ethyl and methyl 2-methyl-5-(D-arafemo-tetrahydroxybutyl)-3-furoate mainly proceeds with inversion at C-l, to afford 5-(l,4-anhydro-D-nbo-tetrahydroxybutyl)-2-methyl-3-furoate. The thermodynamically less stable 1,4-anhydro-D-arabino derivative, in which the configuration is retained, was also produced in low yield. It was further shown that the anhydro derivatives are interconvertible, that is, that the dehydration is a reversible process, although the Iyribo configuration always preponderates. 

A novel synthesis of branched-chain monosaccharides was based on the finding that 3-furoic acid readily undergoes Birch reduction, affording 2,3-dihydro-3-furoic acid. Treatment of its methyl ester 398 with methanol and acid gave,264 in quantitative yield, methyl tetrahy-dro-5-methoxy-3-furoate 399 as a mixture of the isomers. Compounds... 

Some of the simple condensations of a-ketoesters with a-halogenoketones suffer from the disadvantage that mixtures of furans may result. Nakanishi used this reaction in condensing chloroacetaldehyde with ethyl acetoacetate in the presence of pyridine to give the known 2-methyl-3-furoate in 55% yield during the synthesis of an insecticide (70MI31200). 

The ester moiety of methyl 2-methoxy-4-furoates underwent the usual addition reaction with Grignard reagents to provide tertiary alcohols, as exemplified in Equation (172). However, displacement of the 2-methoxy group of the corresponding 3-furoate isomers occurred under the same reaction conditions, presumably via a six-membered organomagnesium chelate, to give 2-substituted-3-furoates as the major products (Equation 173) <2003TL5781>. 

An efficient synthetic sequence for the preparation of 2,4-b/s(trifluoromethyl)furan was developed by R. Filler and co-workers. " The potassium enolate of ethyl 4,4,4-trifluoroacetate was reacted with 3-bromo-1,1,1-trifluoroacetate in DMSO to afford 2,4-bis (trifluormethyl)-4-hydroxydihydro-3-furoate as a result of O-alkylation. Interestingly, under these conditions usually C-alkylation is preferred. Next, dehydration was performed to give the corresponding 2,4-bis (trifluoromethyl)-3-furoate in good yield. Finally, decarboxylation by heating with quinoline and CUSO4 yielded the target furan in excellent yield. 

CH20Me at — 10°C. The corresponding photo-adduct (37) of methyl 2,5-dimethyl-3-furoate rearranges to the diepoxide (38) on heating. The pale... 

The indirect 3-alkylation of 2,5-dimethylfuran was achieved via a tandem Michael addition of a nitroalkane and elimination of nitrous acid starting from cis-3-hexene-2,5-dione, a ring opening product of 2,5-diraethylfuran. Hydrogenation of the carbon-carbon double bond and a subsequent Paal-Knorr reaction provided 3-substituted-2,5-dimethylfurans <01S2003>. Selective ring bromination of methyl 2-methyl-3-furoate with NBS was realized when DMF, an aprotic polar solvent, was used. If the same reaction was carried out in CCI,... 

The Feist-Benary furan synthesis is most commonly used for the preparation of 2-substituted 3-furoates, including ethyl 2-methyl-3-furoate, the original compound prepared by Benary. The resulting ester is generally converted into a carboxylic acid for use in a variety of transformations, including decarboxylation to produce the corresponding 2-substituted furan. For example, reaction of ethyl 7-methyl-3-oxooct-6-enoate with... 

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