Diethyl methylmalonate

Van Leeuwen et al. used several generations of carbosilane dendrimers with 4, 8, 24, and 36 diphenylphosphine end-groups (Figure 4.15) for the allylic alkylation reaction of allyl trifluoracetate with sodium diethyl 2-methylmalonate.[31]... 

The same ligand system was used in the allylic alkylation of allyl trifluoroacetate with sodium diethyl-2-methylmalonate showing a more or less constant conversion over 8 h (20 exchanged reactor volumes). This is in contrast to peripheral functionalized dendrimers (Section 4.4.2), which deactivated at longer reaction times. 

The palladium catalyst supported on the dendrimer with 24 phosphine end groups (2) was used in a CFMR. In the continuous process a solution of allyl trifluoroacetate and sodium diethyl 2-methylmalonate in THF (including -decane as an internal standard) was pumped through the reactor. Figure 4 shows the conversion as a function of the amount of substrate solution (expressed in reactor volumes) pumped through the reactor. The reaction started immediately after the addition of the catalyst, and the maximum conversion was reached after two reactor volumes had passed, whereupon a drop in conversion was observed. It was inferred from the retention of the dendrimer (99.7% in dichloromethane) that the decrease was not caused by dendrimer depletion, and it was therefore ascribed to the... 

A ,Af-Dimethylcyclopropaniminium fluorosulfate reacts with added carbanions such as the sodium salts of methyl 2-methyl-3-oxobutanoate or diethyl 2-methylmalonate in dichloromethane or dichloromethane/dimethyl sulfoxide to give the corresponding aminocyclopropylated species 1 in poor yield. ... 

The reaction of FITS compounds with the sodium salt of 2-methylcyclohexan-l,3-dione led to the 0-perfluoroalkylated and the C-perfluoroalkylated products. The ratio 0-derivatives C-derivatives was strongly dependent upon the reaction temperature, the C-perfluoroalkylated product predominating at lower temperature. Similar results were obtained with ethyl 2-methylacetoacetate. In the case of the sodium salt of diethyl 2-methylmalonate and of 2-nitropropane, only the C-perfluoroalkylated products were isolated. ... 

Rather than pyridine or ammonia, bases such as sodium hydride or sodium ethoxide can be used to generate a malonate enolate anion. Such enolates are easier to control, from a synthetic viewpoint, and allow a wider range of reactions. For this reason, they are collected into this section. An example is the reaction of the sodium enolate of diethyl 2-methylmalonate with the bromine moiety in phthalimide derivative 4.42. This displacement reaction was followed by removal of the phthalimidoyl group, hydrolysis of the esters and decarboxylation to give 2-methyl-6-aminohexanoic acid (4.4J),23 Phthalimide 4.42 was prepared by reaction of 1,4-dibromobutane with potassium phthalimide.23 The length of the carbon chain in the... 

C]7H24N20, 2378-95-2) see Methotrexate diethyl Ai-(5-methylamino-2-thenoyl)-L-glutamate (C15H22N2O5S 112889-02-8) see Raltitrexed diethyl (l-methylbutyl)malonate (C12H22O4 117-47-5) see Secobarbital diethyl methylmalonate... 

The catalytic hydrogenation of 1-piperidinylmethylenemalonate (274, n = 1, X = CH2) over platinum black in glacial acetic acid likewise gave diethyl methylmalonate (64JMC68). 

Cyclization of this acid with stannic chloride in carbon disulfide gave l-keto-l,2,3,4-tetrahydrodibenzothiophene (46) (65%). The 2-methyl analog of 46 has likewise been synthesized from diethyl methylmalon-ate. ... 

Another example of a dendritic effect observed for a core-funtionalized dendritic catalyst was described by Oosterom et al. (19) for allylic alkylation reactions (Section II). The palladium complexes of 5 catalyzed the alkylation of 3-phenylallyl acetate with sodium diethyl methylmalonate. It was observed that the reaction rate decreased and the fraction of branched product increased with increasing generation number. 

A fused tricyclic ring system based on an indole provides yet another NSAID. Michael addition of the anion from diethyl methylmalonate to cyclohexanone followed by acid hydrolysis of the product gives cyclohexanone (21-3), which incorporates the characteristic profen 2-substituted carboxylic side chain. Sequential reaction with para-chlorophenylhydrazine and a strong acid gives the fused indole... 

Alkylation, of diethyl malonate with 3-chlorocyclopentene, 32, 52 of diethyl methylmalonate with M-decyl bromide, 38, 49 of diethyl phthalimidomalonate,... 

Alternative methods of preparing the starting acids can be used, but are generally less convenient. Benzo[6 ]thiophene derivatives were prepared from 2-methyl-3-(2 -thenoyl)propionic acid, which was obtained either by reacting 2-thienylmagnesium iodide with methylsuccinic anhydride, or by coupling 2-bromoacetylthiophene with the sodium salt of diethyl methylmalonate (45JA1645). 

The most detailed results were obtained with ethyl acrylate, which gave varying amounts of the linear product (diethyl succinate) and the branched product (diethyl methylmalonate) depending on the temperature and the gas used (carbon monoxide or nitrogen). The following scheme accounts for their observations ... 

Sterically hindered p-cyano- and / -nitro-a-haloisobutyrophenones (18) have been reported to react with the 2-nitropropane anion by the S l mechanism to form the C-alky-lation product99. However, a p-nitro group is necessary for the reactions with diethyl malonate and diethyl methylmalonate, benzenethiolate and /7-toluenesulphinate ions (equation 29). 

At higher temperatures (about 70°) the diethyl ethoxy-methylmalonate formed tends to eliminate ethanol, forming diethyl methylenemalonate which is hydrogenated to diethyl methylmalonate. 

Diethyl mercaptoacetal, 35, 51 Diethyl methylevemalonate, 38, 22 Diethyl methylmalonate, 38, 49 Diethyl methylphosphonate, 31, 34 Diethyl o mtrobenzoylmalonate, 30, 71 Diethyl oxalate, 34, 13, 37, 71 Diethyl phthahmidobutylmalonate, 32, 15... 

To 250ml ethyl alcohol was added 5-(amidino)methyl-l,3-benzodioxolane (0.23 mol), 50 ml diethyl methylmalonate, 125 ml 25% NaOH in methyl alcohol, and the mixture refluxed 5 hours. The solvent was removed, the residue dissolved in water, acidified with 6 M HCl, and the product isolated by precipitation. 

Chloropyrazine and derivatives have been shown to react with alkali metal derivatives of a phenylacetonitrile or of a phenylacetamide for example, 2-chloropyrazine treated with diphenylacetonitrile in toluene with sodium amide gave 2-(T-cyano-r,r-diphenylmethyl)pyrazine (68, R = H) (1021, 1022). 2-Chloro-5-phenylpyrazine(s) with diethyl methylmalonate and sodium hydride gave 2-(r,l -di(ethoxycarbonyl)ethyl]-5-phenylpyrazine(s) (363-365, 824, 825), and a similar reaction occurred with 2-chloropyrazine (364, 365,1023). 

The first enantioselective total synthesis of (+)-macbecin I was accomplished by R. Baker and co-workers. A key vinyl iodide precursor was prepared stereoselectively using the malonic ester synthesis. Diethyl methylmalonate was treated with in situ generated diiodocarbene in ether at reflux to afford diiodomethylmethylmalonate in good yield. This dialkylated malonic ester then was converted to ( )-3-iodo-2-methyl-2-propenoic acid by reacting it with aqueous KOH. The saponification was accompanied by a concomitant decarboxylation. 

The same type of reaction was observed with 2-chlorocyclohexanone and the sodium salts of dimethyl malonate and diethyl methylmalonate, affording bicyclo[3.1.0]hexan-6-ols (5) and with 2-chlorocycloheptanone and the sodium salts of diethyl malonate and diethyl methylmalonate, affording bicyclo[4.1.0]heptan-7-ols (6). ... 

The synthesis of a- and P-santonins (la,b) has been described by Abe and coworkers [89]. The key intermediate for preparing santonins utilizes eusantonin (38) which is obtained by condensing 3-keto-4,9-dimethyl-l,2,3,7,8,9-hexahydro-naphthalene (37) with diethyl methylmalonate. The two different routes to arrive at a-and P-santonins are given in scheme 1. 

Diethyl methylmalonate, for instance, is formed in 97% yield when diethyl 3-methyl-2-oxosuccinate is heated at 130° until evolution of carbon monoxide ceases.58... 

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