5-Acylation ethyl 2- acetate

The acylation of ketones with esters an example of the Clalsen condensation is generally effected with a basic reagent, such as sodium ethoxide, sodium, sodamide or sodium hy dride. Thus acetone and ethyl acetate condense in the presence of sodium ethoxide to yield acetylacetone ... 

The preparation of benzoylacctone Is another example of the acylation of a ketone (acetophenone) by ethyl acetate to a p diketone (Claisen condensation compare preceding Section) ... 

Norethindrone may be recrystakhed from ethyl acetate (111). It is soluble in acetone, chloroform, dioxane, ethanol, and pyridine slightly soluble in ether, and insoluble in water (112,113). Its crystal stmcture has been reported (114), and extensive analytical and spectral data have been compiled (115). Norethindrone acetate can be recrystakhed from methylene chloride/hexane (111). It is soluble in acetone, chloroform, dioxane, ethanol, and ether, and insoluble in water (112). Data for identification have been reported (113). The preparation of norethindrone (28) has been described (see Fig. 5). Norethindrone acetate (80) is prepared by the acylation of norethindrone. Norethindrone esters have been described ie, norethindrone, an appropriate acid, and trifiuoroacetic anhydride have been shown to provide a wide variety of norethindrone esters including the acetate (80) and enanthate (81) (116). 

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

Normally ethyl acetate is used for the acylation of primary amines, in many cases, as acyl donor and solvent. Other acylating agents such as alkyl methoxy acetates are... 

The chemoenzymatic synthesis of the analgesic U-(—)-50,488 [41] and new C2-symmetric bisaminoamide ligands derived from N,N-disubstituted trans-cyclohexane, ,2-diamine [41] has been possible by a CALB-catalyzed resolution using ethyl acetate as solvent and acyl donor [42]. 

We initially tested Candida antarctica lipase using imidazolium salt as solvent because CAL was found to be the best enzyme to resolve our model substrate 5-phenyl-l-penten-3-ol (la) the acylation rate was strongly dependent on the anionic part of the solvents. The best results were recorded when [bmim][BF4] was employed as the solvent, and the reaction rate was nearly equal to that of the reference reaction in diisopropyl ether. The second choice of solvent was [bmim][PFg]. On the contrary, a significant drop in the reaction rate was obtained when the reaction was carried out in TFA salt or OTf salt. From these results, we concluded that BF4 salt and PFg salt were suitable solvents for the present lipase-catalyzed reaction. Acylation of la was accomplished by these four enzymes Candida antarctica lipase, lipase QL from Alcaligenes, Lipase PS from Burkholderia cepacia and Candida rugosa lipase. In contrast, no reaction took place when PPL or PLE was used as catalyst in this solvent system. These results were established in March 2000 but we encountered a serious problem in that the results were significantly dependent on the lot of the ILs that we prepared ourselves. The problem was very serious because sometimes the reaction did not proceed at all. So we attempted to purify the ILs and established a very successful procedure (Fig. 3) the salt was first washed with a mixed solvent of hexane and ethyl acetate (2 1 or 4 1), treated with activated charcoal and passed into activated alumina neutral type I as an acetone solution. It was evaporated and dried under reduced... 

The catalytic alcohol racemization with diruthenium catalyst 1 is based on the reversible transfer hydrogenation mechanism. Meanwhile, the problem of ketone formation in the DKR of secondary alcohols with 1 was identified due to the liberation of molecular hydrogen. Then, we envisioned a novel asymmetric reductive acetylation of ketones to circumvent the problem of ketone formation (Scheme 6). A key factor of this process was the selection of hydrogen donors compatible with the DKR conditions. 2,6-Dimethyl-4-heptanol, which cannot be acylated by lipases, was chosen as a proper hydrogen donor. Asymmetric reductive acetylation of ketones was also possible under 1 atm hydrogen in ethyl acetate, which acted as acyl donor and solvent. Ethanol formation from ethyl acetate did not cause critical problem, and various ketones were successfully transformed into the corresponding chiral acetates (Table 17). However, reaction time (96 h) was unsatisfactory. 

The strategy for the asymmetric reductive acylation of ketones was extended to ketoximes (Scheme 9). The asymmetric reactions of ketoximes were performed with CALB and Pd/C in the presence of hydrogen, diisopropylethylamine, and ethyl acetate in toluene at 60° C for 5 days (Table 20) In comparison to the direct DKR of amines, the yields of chiral amides increased significantly. Diisopropylethylamine was responsible for the increase in yields. However, the major factor would be the slow generation of amines, which maintains the amine concentration low enough to suppress side reactions including the reductive aminafion. Disappointingly, this process is limited to benzylic amines. Additionally, low turnover frequencies also need to be overcome. 

The analytical method to determine carfentrazone-ethyl and the major animal metabolites (C-Cl-PAc and C-Pac) in bovine matrices is similar to the method for crop matrices. The hexane-aqueous partition to separate carfentrazone-ethyl from the acid metabolites can be replaced by a Cig SPE cartridge. After the SPE, use 12 mL of water-acetonitrile (7 3, v/v) to elute the metabolites and then use 12 mL of hexane-ethyl acetate (4 1, v/v) to elute carfentrazone-ethyl after drying the cartridge. Follow the rest of the respective analytical procedures for carfentrazone-ethyl and the acid metabolites described in Sections 6.3 and 6.4. However, no reflux under boiling is necessary for the analysis of acid metabolites based on a goat metabolism study, because no conjugated acid metabolites were detected. Also, since HM-C-Cl-Pac is not analyzed for in the bovine matrices, no acylation is needed in the method. Analyze the metabolites by GC/MS, and monitor the ions at m/z 362 for C-Cl-Pac and 303 for C-PAc. 

An important group of acylation reactions involves esters, in which case the leaving group is alkoxy or aryloxy. The self-condensation of esters is known as the Claisen condensation.216 Ethyl acetoacetate, for example, is prepared by Claisen condensation of ethyl acetate. All of the steps in the mechanism are reversible, and a full equivalent of base is needed to bring the reaction to completion. Ethyl acetoacetate is more acidic than any of the other species present and is converted to its conjugate base in the final step. The (3-ketoester product is obtained after neutralization. 

The instability of 5-aminoimidazoles (96) has led to in situ acylation being used to obtain stable compounds and using this approach several derivatives have been prepared. For example, a solution of the appropriate 5-nitroimidazole (97) in ethyl acetate was reduced with Raney nickel, and the resulting solution of 5-aminoimidazole (96) then treated with an acid chloride to give the amides (118 R1 = Me, R2 = S02Me, COPh, R3 = alkyl, aryl, hetaryl) (25-45%) [82IJC(B)1087],... 

The complete transformation of a racemic mixture into a single enantiomer is one of the challenging goals in asymmetric synthesis. We have developed metal-enzyme combinations for the dynamic kinetic resolution (DKR) of racemic primary amines. This procedure employs a heterogeneous palladium catalyst, Pd/A10(0H), as the racemization catalyst, Candida antarctica lipase B immobilized on acrylic resin (CAL-B) as the resolution catalyst and ethyl acetate or methoxymethylacetate as the acyl donor. Benzylic and aliphatic primary amines and one amino acid amide have been efficiently resolved with good yields (85—99 %) and high optical purities (97—99 %). The racemization catalyst was recyclable and could be reused for the DKR without activity loss at least 10 times. 

Secondary nitramines are conveniently prepared from the nitrolysis of A, A-dialkylamides with nitronium salts in acetonitrile or ethyl acetate at 20 °C where the acyl group is converted into an acylium tetrafluoroborate (Equation 5.14). Problems can occur if commercial nitronium salts like the tetrafluoroborate are used without purification. The presence of nitrosonium salts can then lead to nitrosamines via nitrosolysis. Yields of secondary nitramine up to 90 % have been reported with solutions of nitronium tetrafluoroborate in acetonitrile di-n-butylnitramine is obtained in 82 % yield from the nitrolysis of corresponding acetamide. ... 

Alkylation of ll-mercaptopyrido[l,2-h]cinnolin-6-ium hydroxide inner salts (e.g., 41) with ethyl bromoacetate gave ll-(ethoxycarbonylmethyl(thio derivatives 64 (R = H), which could be hydrolyzed to the ll-(carboxy-methyl)thio derivative or back to the starting compound 41 (74JHC125). Hydrolysis of the ll-bis(methoxycarbonyl)methylene 66 (R = H), and 2-cyano derivatives of 17 (R = H) in boiling HCl afforded 11-methyl and 2-carboxylic acid derivatives, respectively (74JHC125). The 2-nitro derivative of 17 (R = H) was reduced to the 2-amino derivative over Pd/C with NaBH4 in aqueous methanol, and the 2-amino group was acylated with acetic anhydride at 100°C. 

Asymmetric reductive acetylation was also applicable to acetoxyphenyl ketones. In this case the substrate itself acts as an acyl donor. For example, m-acetoxyace-tophenone was transformed to (R)-l-(3-hydroxyphenyl)ethyl acetate under 1 atm H2 in 95% yield [16] (Scheme 1.12). The pathway of this reaction is rather complex. It was confirmed that nine catalytic steps are involved two steps for ruthenium-catalyzed reductions, two steps for ruthenium-catalyzed racemizations, two steps... 

For the regeneration of ATP, we chose the system based in the use of acetyl phosphate as final phosphoryl donor because this affords several advantages (i) acetyl phosphate is easily obtained by acylation of phosphoric acid with acetic anhydride in ethyl acetate [24], and (ii) the resulting sodium acetate is a non-toxic and an environmentally compatible compound. However, this regeneration system is quite sensitive to pH changes. Thus, a continuous adjustment of the pH to 7.5 is needed to maintain the proper operation of the system. Perhaps the main aspect of this approach is that the DHAP must be formed at the same rate as it is consumed by the aldolase. To avoid the accumulation of DHAP and minimize its non-enzymatic degradation, fine tuning of the aldolase/DHAK activities is needed. This adjustment must be experimentally optimized for some acceptors. 

This reaction presumably proceeds via the acyl chloride, because it is known that triphenylphosphine and carbon tetrachloride convert acids to the corresponding acyl chloride.104 Similarly, carboxylic acids react with the triphenylphosphine-bromine adduct to give acyl bromides.105. Triphenylphosphine/lV-bromosuccinirnide also generates acyl bromides in situ 06 Alcohols can be esterified by heating in excess ethyl formate or ethyl acetate and triphenylphosphine in carbon tetrabromide.107 All these reactions are mechanistically analogous to the alcohol-to-halide conversions that were discussed in Section 3.1.2. 

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