Methyl /?-aminocrotonate

Methoxypyridazine 1-oxide reacts with methyl /3-aminocrotonate in the presence of benzoyl chloride to give a-(6-methoxy-3-pyridazinyl) /3-aminocrotonate (112) which can be converted by mild hydrolysis into the corresponding acetate (113 Scheme 34) <78JHC1425). 

Reaction of 1 mole of aminals 352 with 4 mol of methyl 3-aminocrotonate in the presence of the solid acids montmorillonte clay (Kio) and ZF520 zeolite as strong Bronsted acidic catalysts, gave 1,4-dihydropyridines 353 and 2-methyl-4//-pyrido[l, 2-n]pyrimidin-4-one (99MI8). 

The benzo-fused dihydrotetrazolo[2,7]naphthyridine 308 is a minor end-product of a mixed Hantzsch pyridine synthesis involving 2-azido-3-nitrobenzaldehyde, /3-aminocrotononi trile, and methyl /3-aminocrotonate in ethanol (Scheme 76) <2001TL4507>. 

The reaction of N,N- dimethylaniline with pyridine (equation 55) should also be considered in this category. Enamines usually attack acylated N- oxides at position 2 unless it is blocked, as in 2-methylquinoline 1-oxide, when attack takes place at C-4. Methyl /3-aminocrotonate attacks quinoline and isoquinoline AT-oxides at the position a to the N- oxide function in the presence of tosyl chloride (78JHC1425). However, pyridine and 2-methylpyridine 1-oxides react at the 4-position (equation 142). A low yield of by-product (242) is formed in each case, probably as a result of self-condensation of methyl /3-aminocrotonate. 4-Hydroxyquinoline 1-oxide is exceptional in that it reacts with an enamine in the presence of tosyl chloride at the /3-position (Scheme 170) (B-71MI20500). 5-Amino-3-methylisoxazole reacts with quinoline 1-oxide at the a-position, and the product can be degraded, to afford ultimately 2-methylquinoline (Scheme 171) (78CPB2759). 

Khadilkar, B.M., Gaikar, V.G. and Chitnavis, A.A., Aqueous hydrotrope solution as a safer medium for microwave enhanced Hantzsch dihydropyridine ester synthesis, Tetrahedron Lett., 1995, 36, 8083-8083 Khadilkar, B.M. and Chitnavis, A.A., Rate enhancement in the synthesis of some 4-aryl- 1,4-dihydropyridines using methyl 3-aminocrotonate, under microwave irradiation, Indian J. Chem., Sect. B, 1995, 34, 652-653. 

Another application of additions to chiral vinylic sulfoxides constitutes the Hantzsch-type reaction of methyl 3-aminocrotonate with compound (109), yielding the dihydropyridine derivative (110) as a single... 

Methyl 3-aminocrotonate reacts with Appel salt 20 to give isothiazole 67 in high yield (78%) (Scheme 5) <1998J(P1)77>. The spontaneous conversion of the presumed intermediate 68 into the isothiazole also requires nucleophilic attack on the S-l atom. 

Aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-l,4-dihydropyridine (amlodipine) was prepared from 2-(phthalimidoaminoethoxy)acetoacetate, 2-chlorobenzaldehyde and methyl-3-aminocrotonate under refluxing in ethanol for 24 hours. The ketoester was prepared by the method of Troostwijk and Kellog (JCS Chem. Comm., 1977, p.932). Methyl-3-aminocrotonate can be prepared by known method. Phthalimido-amino-protecting group was removed using hydrazine hydrate in ethanol at the reflux temperature. 

Piperidinedione with methyl 3-aminocrotonate and p-nitrobenzaldehyde (128) gave methyl 2-methyl-5-oxo-4-p-nitrophenyl-1,4,5,6,7,8-hexahydro-l,6-naphthyridine-3-carboxylate (129) (reactants, MeOH, reflux, 7h 65%) analogs likewise.869... 

Since its discovery in 1985, Appel salt 770 has been exploited for nucleophilic displacement reactions. For example, it reacts readily with amines, e.g., Scheme 150 <2002J(P1)1535> (or hydrazine <1996TL3709>), a more exotic example being its reaction with methyl 3-aminocrotonate resulting in formation of an isothiazole 771 (Scheme 151) <1998J(P1)77>. 

According to Bucha et al. (1962), the synthesis of isocil is effected by reacting isopropyl isocyanate with methyl 3-aminocrotonate to form methyl 3-(3-butyIureido)crotonate, which is cyclised without isolation by heating in 6% sodium hydroxide. The uracil is then precipitated by acidification and brominated to give the end-product. 

A mixture of 0.34 g methyl 3-aminocrotonate (3 mmol) and 0.63 g 4,5-dichloro-1,2,3-dithiazolium chloride (3 mmol) in 25 mL dichloromethane was stirred at room temperature for 1 h after which 0.49 mL pyridine (6 mmol) was added. The mixture was stirred for a further 30 min. The product was separated by flash chromatography on silica gel, eluting with dichloromethane/light petroleum (1 3) to give 0.43 g methyl 5-cyano-3-methylisothiazole-4-carboxylate, in a yield of 78%. Colorless crystals can form from dichloromethane-light petroleum, m.p. 55 - 56°C. 

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