Methyl 4-bromocrotonate

The 3,4-dihydrodiol of BcP was synthesized from 4-oxo-l,2,3,4-tetrahydro-BcP (15) by Method I (66). The ketone L was itself prepared from 4-oxo-l,2,3,4-tetrahydrophenanthrene via a multistep sequence entailing Reformatsky reaction with methyl bromocrotonate, dehydration of the resulting alcohol, isomerization to the aryl-butyric acid, and cyclization of its acid chloride with SnCl - Full... 

Among early reported Pd-catalyzed reactions, the Mori-Ban indole synthesis has proven to be very useful for pyrrole annulation. In 1977, based on their success of nickel-catalyzed indole synthesis from 2-chloro-fV-allylaniline, the group led by Mori and Ban disclosed Pd-catalyzed intramolecular reactions of aryl halides with pendant olefins [122]. Compound 102, easily prepared from 2-bromo-lV-acetylaniline and methyl bromocrotonate, was adopted as the cyclization precursor. Treatment of 102 with Pd(OAc)2 (2 mol%), Ph3P (4 mol%) and NaHCQ3... 

The role of the solvent in practically all of the reactions so far discussed is decisive. For example, allylic halides having electron-attracting substituents, such as methyl bromocrotonate, upon treatment with nickel carbonyl in hydroxylic solvents do not react with CO. Instead substitutive hydrogenation of the halogenated carbon atom occurs (55), while in ketonic solvents the products which might be expected from the carbonylation of normal allylic halides are obtained (50). 

Uses Solvent for paints, electrochemistry, polymer and boron chemistry, physical processes such as gas absorp., extraction, stabilization, industrial prods, such as fuels, lubricants, textiles, pesticides process solvent/solubilizer pharmaceutical solvent, vehicle in the Reformatsky reaction with methyl bromocrotonate Manuf./Distrib. Aldrich Brand-Nu Eabs Ferro/Grant Fluka Sigma Spectrum Quality Prods. 

METHYL y-BROMOCROTONATE JV-Bromosuccinimide. Dissolve, with the aid of rapid mechanical stirring, 80 g. of pure succinimide (Section V,14) in a mixture of 150 g. of finely crushed ice and a solution of 32 g. of sodium hydroxide in 200 ml. of water contained in a litre beaker and cooled externally by ice. Immediately the imide has dissolved, continue the vigorous stirring and introduce 42 -5 ml. of bromine in one lot from a separatory funnel supported over the beaker it is essential that the bromine be instantly suspended in the solution. After stirring vigorously for 2 minutes, filter at the pump and... 

Methyl y-bromocrotonate. Mix 36 g. of iV-bromosuccinimide, 40 g. of methyl crotonate and 60 ml. of dry, redistilled carbon tetrachloride in a 500 ml. round bottomed flask. Reflux ou a water bath for 12 hours by this time all the sohd should have risen to the surface of the liquid. Filter off the succinimide at the pump and wash it with a little dry carbon tetrachloride. Remove the solvent on a water bath and distil the residue under reduced pressure, preferably from a Widmer flask (compare Figs. II, 24, 4-5). Collect the methyl y-bromocrotonate at 77-78°/8 mm. the yield is 31 g. 

Methyl crotonate reacts with NBS and brominates is allylic position giving methyl 3-bromocrotonate, a valuable synthetic reagent used in Reformatsky reaction. 

Cyclopropane ring formation has been brought about by Michael addition initiated ring closure (sometimes called MIRC). The reaction of methyl 4-bromocrotonate (3) with different nucleophiles either gives the SN2-displacement product 4 or the Michael addition intermediate 5 which finally forms the cyclopropane carboxylate 697 (the configuration of 6 has not been determined). This reaction has been studied with different nucleophiles in the solvent systems tetrahydrofuran-HMPA (20 1) and tetrahydrofuran the bromocrotonate 3 was reacted with 1 equivalent of a 1 M solution of the lithium enolates at —78 for 12 h at room temperature97. 

The dependence of the counterion and of the solvent99 was studied in the addition of sec-butyl and tert-butyl mercaptide to methyl 4-bromocrotonate (3). The highest yield of the Michael addition induced cyclopropane product 10 was observed with lithium as counterion in dichloromethane or pentane as solvent. 

Lastly, a formal synthesis of almotriptan (5) has been published by the Bosch group in Spain using an intramolecular Heck approach (Scheme 23). lodination of aniline 58 with bis(pyridine)iodonium(I) tetrafluoroborate followed by reaction with trifluoroacetic anhydride (TFAA) gave the o-iodotrifluoroacetanilide 66. Alkylation of 66 with methyl 4-bromocrotonate afforded 67, which underwent palladium catalyzed... 

Methyl n-amyl carbinol. 247, 254 Methyl n-amyl ketone, 482 Methylaniline (mono), pure, from commercial methylaniline, 562, 570 P-Methylanthraquinone, 728, 740 Methyl benzoate, 780, 781 p-Methyl benzyl alcohol, 811,812 Methyl benzyl ketone, 727, 735 Methyl y-bromocrotonate, 926, 927 2-Methyl-2-butene, 239 Methyl n-butyl carbinol, 247,255 Methyl n-butyl ether, 314 Methyl n-butyl ketone, 475, 481 4-Methylcarbostyril, 855 p-Methylcinnamic acid, 719 4-Methylcoumarin, 853, 854 Methyl crotonate, 926, 927 Methylethylacetic acid, 354, 358 Methylethylethynyl carbinol, 468 Methyl ethyl ketone, 335, 336 purification of, 172 Methyl n-hexyl ether, 314 Methyl n-hexyl ketone, 335, 336 Methyl n-hexyl ketoxime, 348 Methyl hydrogen adipate, 938 Methyl hydrogen sebacate, 938,939 4-Methyl-7-hydroxycoumarin, 834 Methyl iodide, 287 Methyl isopropyl carbinol, 247,255 Methyl 4-keto-octanoate, 936... 

Methyl derivatives of 2-oxo-2//-pyrido[l,2-a]pyrimidines were prepared by Kato et al.19 and Potts et al.2 by using 2-bromocrotonic acid and ethyl tetrolate, respectively. 

Two simple applications may be mentioned. With cyclohexene, 3-bromo-cyclohexene is obtained in a satisfactory yield (Expt 5.68), the latter upon dehydrobromination with quinoline affords an 80-90 per cent yield of cyclo-hexa-1,3-diene (Expt 5.13). Methyl crotonate yields the valuable synthetic reagent methyl y-bromocrotonate (Expt 5.69) this latter compound permits the introduction (in moderate yield) of a four-carbon atom chain at the site of the carbonyl group by the use of the Reformatsky reaction (compare Expt 5.170) ... 

Experiment 5.69 METHYL y-BROMOCROTONATE (Methyl 4-bromobut-2-enoate)... 

Fig. 1.31. The Wohl-Ziegler bromination of crotonic acid methyl ester D exclusively supplies the bromocrotonic ester G. However, vinyl acetic acid ester C and NBS exclusively yield the dibromo addition product B under Wohl-Ziegler conditions. Here, NBS acts as a Br2 source for addition rather than substitution. The fact that vinyl acetic acid ester and NBS do not react likewise to yield the bromocrotonic ester G is due to an electronic effect discussed in the text.

Fig (23) Acid (193) prepared from bromoanisole (190) by standard organic reactions, undergoes cyclization with polyphosphoric acid leading the formation of tetralone (194). A Reformatsky reaction on compound (194) with methyl g-bromocrotonate followed by aromatization produces compound (195). It is converted to compound (196) by treatment with methylmagnesium and cyclization. The corresponding phenol was oxidized to miltirone (197). 

The overall rate of elimination of methyl 4-bromocrotonate was found to be significantly higher than that of methyl 4-bromobutyrate (Table 22)171. The participation by the COOCH3 group is more effective as predicted67 because of the high polarity of the allylic C—Br bond in the transition state. The pyrolysis, under maximum inhibition, gave parallel reactions as described in equation 77. 

Participation of the COOCH3 in the pyrolysis of methyl u-(bromomethyl)benzoate was believed to be the reason why it decomposes much faster than methyl 4-bromocrotonate to yield phthalide and CH3Br. Unfortunately, attempts to prepare the benzoate yielded phthalide. An intimate ion-pair mechanism as in methyl co-chloro and co-bromo esters (equation 74) was suggested. 

Methyl 4-bromocrotonate was purchased from Lancaster Synthesis Inc. and distilled before use. 

Methyl 4-bromocrotonate Crotonic acid, 4-bromo-, methyl ester (8) 2-Butenoic acid, 4-bromo-, methyl ester (9) (1117-71-1)... 

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