Methyl chloroformate reaction

In an early synthesis a methyl carbonate, prepared by reaction of a phenol with methyl chloroformate, was cleaved selectively in the presence of a phenyl ester. ... 

A synthesis for the enantiomerically pure 535 was developed starting with D-phenylalanine which upon reaction with methyl chloroformate gave 528 whose reaction with methoxylamine afforded 529. Cyclization with bis(trifluoroacetoxy)iodobenzene in presence of trifluoroacetic acid gave the tetrahydroquinoline derivative 530 which was demethoxylated to give 531. Treatment of 531 with either benzyl chloroformate or... 

Although this reaction can be carried out at higher temperatures, the yields are reduced, probably owing to loss of the volatile methyl chloroformate, b.p. 71°, and/or decomposition of the product. For example, the yields of trichloromethyl chloroformate are ca. 75% and 55% when the chlorination is carried out at 50-55° and 85-90°, respectively. 

The chlorination of methyl chloroformate in sunlight was first reported by Hentschel, but without a detailed description of either the procedure or the results. The first step of the present procedure for the preparation of trichloromethyl chloroformate utilizes an ultraviolet light source and affords a simple and reproducible way to obtain this reagent. Although trichloromethyl chloroformate may also be synthesized by photochemical chlorination of methyl formate,the volatility of methyl formate causes losses during the reaction and increases the hazard of forming an explosive mixture of its vapor and chlorine gas. The preparation of trichloromethyl chloroformate by chlorination of methyl chloroformate in the dark with diacetyl peroxide as initiator has been reported. However, the procedure consists of several steps, and the overall yield is rather low. 

Alternatively, two phosgene equivalents were studied, methyl chloroformate and p-nitrophenyl chloroformate. When methyl chloroformate was used for the end game, N-carbamate 54 was obtained smoothly but subsequent cyclization to ben-zoxazinone 1 was sluggish. Furthermore, removal of the unreacted intermediate methyl carbamate 54 from Efavirenz was not trivial, thus we did not pursue this method. On the other hand, reaction of 53 and p-nitrophenyl chloroformate initially provided the corresponding p-nitrophenyl carbamate 55 under mild basic conditions (KHC03). Carbamate 55 was smoothly cyclized to 1 upon increasing... 

Dining its preparation by heating dimethyl sulfide and methyl chloroformate in a glass pressure bottle at 80°C, it is essential to interrupt the reaction after 4 h, cool and release the internal pressure of carbon dioxide, before recapping the bottle and heating for a further 22 h. This avoids the possibility of excessive pressure build-up and failure of the cap seal. 

The reaction of pyrazine and quinoxaline with methyl chloroformate and bis-silyl enol ethers gave fused tetrahydropyrazine lactones 88, in an extension of previous work. There was little consistency with the variation of R in the stereochemistry of the products <06T12084>. 

The activation of the hydrazines 397 (Scheme 68) with l,l -carbonyldiimidazole (CDI) and reaction with hydroxylamines gave the hydroxy semicarbazides 398, which could be treated with methyl chloroformate in the presence of TEA to give the first examples of 4-amino-substituted l,2,4-oxadiazolidin-3,5-diones 399 <2000HC055>. 

Starting from 2,4,6-octatriene and pivaldehyde, the conjugated homoallylic alcohol 8 is obtained as the sole product. Cycloheptatriene-derived complexes react with aldehydes and C02 to afford mixtures of the isomeric 1,3- and 1,4-cycloheptadienyl carbinols or acids, respectively. Interestingly, analogous reactions with methyl chloroformate or dimethyl carbamoyl chloride produce the conjugated dienyl ester 9 or amide 10 as unique products [19,20]. 

Many substances react in the gas phase rather than in solution. An important example is the process thought to deplete the ozone layer the reaction between gaseous ozone, O3, and chlorine radicals, high up in the stratosphere. Ultimately, the chlorine derives from volatile halocarbon compounds, such as die refrigerant Freon-12 or the methyl chloroform thinner in correction fluid. 

Hydrazines of type 89 react with various carbonic acid derivatives to furnish cyclized product. Under basic conditions (KOH), in the presence of carbon disulfide or arylisothiocyanates, the cyclized thione 90 is obtained (Scheme 7) <1966JOG3528, 1984JCCS315>. Analogous reactions performed in the absence of base gave 91 as a 3-thiol when performed with carbon disulfide, as a 3-hydroxyl with methyl chloroformate, or as a 3-arylamino with arylisothiocyanates in the presence of dicyclohexylcarbodiimide (Scheme 7) <1986JHC1339, 1992IJB467>. 

The reagent, b.p. 127-130°, is prepared by reaction of allyl alcohol in ether with methyl chloroformate and pyridine (86% yield). 

Terminal allenes.1 A synthesis of 1,2-dienes (3) from an aldehyde or a ketone involves addition of ethynylmagnesium bromide followed by reaction of the adduct with methyl chloroformate. The product, a 3-methoxycarbonyloxy-l-alkyne (2), can be reduced to an allene by transfer hydrogenolysis with ammonium formate catalyzed by a zero-valent palladium complex of 1 and a trialkylphosphine. The choice of solvent is also important. Best results are obtained with THF at 20-30° or with DMF at 70°. 

The addition of a-lithiomethoxyallene 144 [55] to benzaldehyde dimethylhydra-zone 145 (Eq. 13.48) leads to a mixture of pyrroline 146 and dihydroazete 147 [56]. The cydization in this case, which takes place in the same operation as the addition to the hydrazone, follows two distinct pathways, with attack of the nitrogen atom taking place at the inner, in addition to the terminal, carbon atom of the allene. A similar reaction of 144 with SAMP-hydrazone 148 (Eq. 13.49) leads to 3-pyrroline 149 in 88% yield and excellent diastereoselectivity [57]. Cleavage of the chiral auxiliary group from 149 takes place in two steps (1, methyl chloroformate 2, Raney nickel, 50 bar, 50 °C) in 74% overall yield. When the addition of 144 to 148 is conducted in diethyl ether, cydization of the adduct does not take place. Surprisingly, the hydrazones of aliphatic aldehydes react with 144 in poor yield in THF, but react quantitatively and diastereoselectively in diethyl ether to give the (uncyclized) allenyl hydrazone products. 

Kahn and Chen (87TL1623) performed the regio- and stereospecific reaction of 1,3-cyclooctadiene and acyliminium derivative 79, which resulted exclusively in compounds 80 in 37% yield after chromatographic purification. 79 was prepared by treatment of the A-methylimine of benzal-dehyde with methyl chloroformate in the presence of titanium(IV) chloride. 

Comparison of the configuration of the stannane with the prodncts of reaction reveals that primary alkyl halides that are not benzyhc or a to a carbonyl react with inversion at the lithium-bearing carbon atom. In the piperidine series, the best data are for the 3-phenylpropyl compound, which was shown to be >99 1 er. In the pyrrolidine series, the er of the analogous compound indicates 21-22% retention and 78-79% inversion of configuration. Activated alkyl halides such as benzyl bromide and teri-butyl bromoacetate afford racemic adducts. In both the pyrrolidine and piperidine series, most carbonyl electrophiles (i.e. carbon dioxide, dimethyl carbonate, methyl chloroformate, pivaloyl chloride, cyclohexanone, acetone and benzaldehyde) react with virtually complete retention of configuration at the lithium-bearing carbon atom. The only exceptions are benzophenone, which affords racemic adduct, and pivaloyl chloride, which shows some inversion. The inversion observed with pivaloyl chloride may be due to partial racemization of the ketone product during work-up. 

Less extended investigations have been carried out for the stereochemistry of further substitution reactions, which mostly proceed with lower regioselectivities a-carboxylation (inversion) reaction with methyl chloroformate in the a-position (inversion) a-acylation by 2,2-dimethylpropanoyl chloride (inversion)" y-methylation by methyl iodide (anti-S g) and methyl triflate syn-S f° , intramolecular reactions with allyl chlorides (a, inversion or y, awh -S see Section IV.C.3). 

In a typical synthesis, reduction of the nitro group in starting material 1 leads to the corresponding diamine 1. Reaction with intermediate 12 obtained by acylation of the methyl ether of thiourea with methyl chloroformate, leads directly to fenbendazole (78). ... 

Crich and Rumthao reported a new synthesis of carbazomycin B using a benzeneselenol-catalyzed, stannane-mediated addition of an aryl radical to the functionalized iodocarbamate 835, followed by cyclization and dehydrogenative aromatization (622). The iodocarbamate 835 required for the key radical reaction was obtained from the nitrophenol 784 (609) (see Scheme 5.85). lodination of 784, followed by acetylation, afforded 3,4-dimethyl-6-iodo-2-methoxy-5-nitrophenyl acetate 834. Reduction of 834 with iron and ferric chloride in acetic acid, followed by reaction with methyl chloroformate, led to the iodocarbamate 835. Reaction of 835 and diphenyl diselenide in refluxing benzene with tributyltin hydride and azobisisobutyronitrile (AIBN) gave the adduct 836 in 40% yield, along with 8% of the recovered substrate and 12% of the deiodinated carbamate 837. Treatment of 836 with phenylselenenyl bromide in dichloromethane afforded the phenylselenenyltetrahydrocarbazole 838. Oxidative... 

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