Dimethylamine reaction with esters

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

The cyanobromide (371) was condensed with the bc portion (347) to give the thioether (372) sulfide contraction to give (373) was accomplished using tris(/3-cyanoethyl) phosphine, and with phosphorus pentasulfide the thiolactam-thiolactone (374) was produced. After treatment with Meerwein s salt, reaction with dimethylamine opened the lactone with concomitant formation of an exocyclic methylene group, and subsequent treatment with cobalt chloride or iodide gave the chelate (375) which was reacted with diazabicyclononane to give bisnorcobyrinic add [Pg.435]

Acetal esters such as diethoxyacetic ester and /3,/S-diethoxypropionic ester are readily converted to amides with concentrated ammonium hydroxide. The former ester gives an N,N-dimethylamide by reaction with dimethylamine. ... 

This approach to the synthesis of the 4-dimethylaminobutyrate ester (50, R = (CH2)3NMe2) involved initial reaction of pristinamycin 11 with 4-chloro-butyroyl chloride in the presence of dimethylaniline yielding the 4-chlorobutyr-ate ester (50, R = (CH2)3C1, 32%), followed by reaction with dimethylamine in methanol at 40 °C. This did indeed provide the required semi-synthetic pristinamycin 11 derivative (50, R = (CH2)3NMe2), which was soluble in water as its hydrochloride salt, but the yield was low (5%). The use of alternative secondary amines in the final reaction did not result in any improvement in the yield. 

N values at low dimethylamine ratios confirmed that little direct acyl addition was observed. Figure 3 shows a summary of the most probable reaction pathways. The low observed MeOH values in the dimethylamine case are in contrast to the previously studied imidization reaction with methylamine, where molar ratios of gaseous reaction products were 0.50/0.026/0.84/1.10-Trimethylamine/Dimethylamine/H2O/MeOH, indicating either predominant elimination of MeOH from esters adjacent to initially formed acid (salts) or, more likely, formation of the amic-acid pair with elimination of MeOH by a neighboring group effect in the case of the primary amine, but essentially NO diacid formation (Figure 4). 

An important feature of polymer synthesis by the active ester method is that displacement of the polymer-bound activating 0eaving) groups can be readily monitored by IR qiectroscopy of the polymer. Tl% IR spectrum generally shows the disappearance of the phenyl ester carbonyl at about 1760 cm, and the appearance of a new carbonyl absorption at 1620-80 cm (amide) and/or 1720-30 cm (ester), together with other characteristic absorptions due to A and A. In some cases, a relatively weak polystyrene band at ca. 1607 cm is also observed. A typical illustration is provided by Fig. IS, showing the amino-lysis of the activated polymer with 6-tert.-butoxycarbonylaminohexylamine, followed by reaction with dimethylamine (see the first entry in Table 7). 

For CAPB, the first step is a reaction of 3-aminopropyl-dimethylamine (DMAPA) with either fatty acids, fatty acid methyl esters, or directly with natural fats (fatty acid glycerin esters). The predominant source oils used determine the fatty acid composition of the betaine, which corresponds to that of the oil. Table 12.3 outlines the typical fatty acid composition of CAPB. 

Spending f-butylcarboxy anhydride (B0C2O). Hydrogenolysis (H2 with Pd/C) permitted the removal of the benzyl protecting group, and the half-acid ester underwent decarboxylation. A Mannich reaction with formaldehyde in the presence of NJ -dimethylamine followed by deprotection (removal of the THP protecting group) resulted in hydroxydiene formation. 

Just as amines react with esters to form amides, lactones react with amines to give lactams or are opened to give amino acid derivatives directly. When P-propiolactone (2.20) reacted with ammonia, for example, 3-aniinopropanamide (2.2Ia) was obtained. 2 Similar reaction with methylamine gaveno2.2/h but rather a 97% yield of 3-aminopropanoic acid, 2.22. Dimethylamine, however, converted 2.20 to 2.2Ic in 79% yield, along with 13% of 2.22.12... 

Considerable effort has been directed to the study of the course of the reaction between chromone-2-carboxylic esters and various amines. Some rather surprising differences have been recorded, such as the types of products (86) and (87), obtained by the reaction of the unsubstituted ethyl ester with dimethylamine and diethylamine respectively [150-152], Jerzmanowska and Kostka [152] suggest that steric factors prevent the attack by a second molecule of diethylamine, and that the course of the reaction with dimethyl-amine is as shown in Figure 2.11. 

On the other hand, reaction of the sulfonyl chloride 397 with excess morpholine, pyrrolidine and piperidine (three equivalents) afforded a mixture of the sulfonamides 400 and 401. The succinimidosulfonamide 401 was formed by simultaneous nucleophilic substitution at sulfur and Michael addition of the amine to the activated alkenic double bond. The pure maleimidosulfonamide 400 could be prepared by column chromatography of the mixture. The reaction of N- p-chlorosulfonylphenyl) maleimide 397 with excess dimethylamine or diethylamine in methanol as solvent resulted in the formation of ring-opened products. For instance, in the reaction with diethylamine, the methyl ester 402 was formed by base-catalysed nucleophilic ring-opening by the solvent (methanol) this ring... 

For the regioselectivity similar rules as for the ester pyrolysis do apply. With simple, alkylsubstituted amine oxides a statistical mixture of regioisomeric olefins is obtained. On the other hand with cycloalkyl amine oxides the regioselectivity is determined by the ability to pass through a planar, five-membered transition state. This has been demonstrated for the elimination reaction of menthyl dimethylamine oxide 10 and neomenthyl dimethylamine oxide 11 ... 

Vinamidinium salts have been used for the preparation of 2,3- or 2,5-disubstituted pyrroles. Thus, reaction of sarcosine ethyl ester with 18 results in an amine-exchange reaction at the least hindered position. Anion mediated cyclization and elimination of dimethylamine leads to 19 <96T6879>. 

Reaction of 4-chloro-6-fluoropyrido[3,4- pyrimidine 59 with [3-methyl-4-(pyridin-3-yloxy)phenyl]amine 60, followed by coupling the formed amine 61 with (3-azabicyclo[3.1.0]hex-6-yl)carbamic acid fi r7-butyl ester, afforded the substituted derivative 62 <2002EPP1249451>. Compound 59 was also reacted with 3-bromoaniline to give the 4-anilino derivative 63 that upon treatment with either methyl- or dimethylamine gave the corresponding 4,6-diamino derivatives 64 (Scheme 2) <1997W09726259, 1995W09519774>. 

The Cope rearrangement of 24 gives 2,6,10-undecatrienyldimethylamine[28], Sativene (25j[29] and diquinane (26) have been synthesized by applying three different palladium-catalyzed reactions [oxidative cyclization of the 1,5-diene with Pd(OAc)2, intramolecular allylation of a /i-keto ester with allylic carbonate, and oxidation of terminal alkene to methyl ketone] using allyloctadienyl-dimethylamine (24) as a building block[30]. 

Synthesis (Kleemann et al. 1999, Janssen (Janssen), 1973 Janssen et al. (Janssen), 1973, Stokbroekx et al., 1973, Niemegeers et al., 1974) ) Treatment of 2-oxo-3,3-diphenyl-tetrahydrofuran, synthesized by treatment of diphenyl-acetic acid ethyl ester with ethylene oxide, with HBr(gas) yields bromo derivative i, which is then converted into butyryl chloride derivative ii by means of thionyl chloride in refluxing chloroform. Reaction of derivative ii with dimethylamine in toluene affords dimethyl (tetrahydro-3,3-diphenyl-2-furylidene)ammonium bromide, which is then condensed with 4-(4-chlorophenyl)-4-piperidinol by means of Na2C03 and Kl in refluxing 4-methyl-2-pentanone to provide loperamide. 

The analysis of polymeric and gaseous products of the reaction of PMMA and di-methylamine at low dimethylamine levels shows that there was a clean reaction that produced 1 eq of anhydride (NOT Amide) per 1 eq of dimethylamine and per 1 eq of MMA. Note that this is in most close agreement with pathway 2a- 3a (Figure 2) in which most of the MMA carbonyls have been converted to COOH or alkylammonium COO salts followed by closure to anhydride. This shows that direct acyl addition (2c— 3c) to form amide, or reaction of carboxylate with adjacent ester (2b- 3b) to form anhydride (which liberates MeOH after proton transfer, and requires only 0.5 eq. dimethylamine per MMA group) are not the predominant pathways under these conditions. The Flory limit effect is consistent with random initial MAA formation, which after cyclization to anhydride (Figure 2) eventually leads to some groups trapped between rings which remain in the uncyclized acid form. 

Substitution of the phosphinate ester group by dimethylamine via the chloride, and thionation of the P=0 group of the 2-phosphabicyclo[2.2.2]octane P-oxide derivatives 28 with diphosphorus pentasulfide affords the corresponding amide 29 and P-sulfide 30 (Scheme 10). The thionation is also achieved with Lawesson s reagent [7,8]. Thermolysis of 28 proceeds a retro Diels-Alder reaction to give 31. 

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