Carbamates from ethyl chloroformate

The carbamates, derived from the reaction of 8-aminoquinoline with phenyl or ethyl chloroformate, upon reduction with NaBH4 gave the... 

Thus, treatment of the benzamide (35-1) from 2-phenethylamine with phosphorus oxychloride probably results in an initial formation of a transient enol chloride this then cycUzes to (35-2) under reaction conditions. The imine is then reduced with sodium borohydride. Resolution by means of the tartrate salt affords (35-3) in optically pure form. Acylation of that intermediate with ethyl chloroformate leads to carbamate (35-4). Reaction of this last with the anion from chiral quiniclidol (35-5) interestingly results in the equivalent of an ester interchange. There is thus obtained the anticholinergic agent solifenacin (35-6) [40]. 

Amines. The common impurities found in amines are nitro compounds (if prepared by reduction), the corresponding halides (if prepared from them) and the corresponding carbamate s ts. Amines are dissolved in aqueous acid, the pH of the solution being at least three units below the pK value of the base to ensure almost complete formation of the cation. They are extracted with ethyl ether to remove neutral impurities and to decompose the carbamate salts. The solution is then made strongly alkaline and the amines that separate are extracted into a suitable solvent (ether or toluene) or steam distilled. The latter process removes coloured impurities. Note that chloroform cannot be used as a solvent for primary amines because, in the presence of alkali, poisonous carbylamines are formed. However, chloroform is a useful solvent for the extraction of heterocyclic bases. In this case it has the added advantage that while the extract is being freed from the chloroform most of the moisture is removed with the solvent. 

Pyrazino[l,2-c]pyrimidines are most commonly prepared from the intermediate 1-alkyl-3-(2-alkylaminoethyl)piperazines (281). This intermediate is readily prepared in three steps from either benzyloxycarbonylsarcosylaspartate (71JMC929) or from iV-benzylethyl-enediamine and diethyl fumarate (75JMC913). Condensation of the piperazine intermediate (281) with ethyl chloroformate at pH 3-3.5 gives the monocarbamates (282). Cyclization of these carbamates by treatment with sodium ethoxide gives the desired ring system (283) (75JMC913). 

The cyclohexene 121, which was readily accessible from the Diels-Alder reaction of methyl hexa-3,5-dienoate and 3,4-methylenedioxy-(3-nitrostyrene (108), served as the starting point for another formal total synthesis of ( )-lycorine (1) (Scheme 11) (113). In the event dissolving metal reduction of 121 with zinc followed by reduction of the intermediate cyclic hydroxamic acid with lithium diethoxyaluminum hydride provided the secondary amine 122. Transformation of 122 to the tetracyclic lactam 123 was achieved by sequential treatment with ethyl chloroformate and Bischler-Napieralski cyclization of the resulting carbamate with phosphorus oxychloride. Since attempts to effect cleanly the direct allylic oxidation of 123 to provide an intermediate suitable for subsequent elaboration to ( )-lycorine (1) were unsuccessful, a stepwise protocol was devised. Namely, addition of phenylselenyl bromide to 123 in acetic acid followed by hydrolysis of the intermediate acetates gave a mixture of two hydroxy se-lenides. Oxidative elimination of phenylselenous acid from the minor product afforded the allylic alcohol 124, whereas the major hydroxy selenide was resistant to oxidation and elimination. When 124 was treated with a small amount of acetic anhydride and sulfuric acid in acetic acid, the main product was the rearranged acetate 67, which had been previously converted to ( )-lycorine (108). 

Carbamate intermediate 7 derived from aminothiophenes 1 and ethyl chloroformate were converted into 3-substituted thieno[2,3-d]pyrimidine-... 

Two synthetic routes for 3-[4-[4-(2-methoxyphenyl)piperazin-l-yl]butyl]-thieno[3,4-d]pyrimidine-2,4-dione 316 were described by Russell et al. (90JHC1761). Carbamate 310a, prepared by treating a mixture of amine hydrochloride 309 and ethyl chloroformate with dilute sodium hydroxide, was reacted with 4-[(2-methoxyphenyl)piperazin-l-yl]butanamine 313 in the presence of trimethylaluminum/toluene. The yield of 316 was a modest 20%. However, when bromobutyl urea 314 was heated with l-(2-methoxyphenyl)piperazine hydrochloride 315 in the presence of sodium bicarbonate and sodium iodide in propan-2-ol, compound 316 was obtained in 84% yield. The first route was also used to synthesize thieno[3,4-d]py-rimidine-2,4-dione 312 in 36% yield from 310a and 4-(2-methoxyphenyl)-1-piperazinethanamine 311. 

Acylation of the well-known Bischler-Napieralski product, 1-benzyl-3,4-dihydroisoquinoline, with ethyl chloroformate gave a mixture of two carbamates, E isomer 118 and Z isomer 119 in the ratio of 1 2, which were readily assigned from their UV and NMR spectra and underwent cycliza-tion on irradiation under either nonoxidative or oxidative conditions to afford the 8-oxoberbine 120 or aporphine skeleton 121 (104,105). Irradiation of either the E or Z enamide, (118 or 119) or their mixture quickly... 

The major cycloadduct 29 readily separable from 30 by recrystallization, underwent catalytic hydrogenation to give the amino alcohol hydrochloride 31 which was in turn selectively N-acylated with ethyl chloroformate affording the carbamate 32 in 84% overall yield. Chlorination of 32 with thionyl chloride and excess of pyridine in chloroform at reflux yielded the chloride 33 (55%) along with a byproduct assigned the dicycloheptyl sulfite 34 (28%). Similarly, treatment of 35, prepared from 31, with thionyl chloride and pyridine gave 36 (36%) and 37 (38%). 

Alkyl esters are efficiently dealkylated to trimethylsilyl esters with high concentrations of iodotrimethylsilane either in chloroform or sulfolane solutions at 25-80° or without solvent at 100-110°.Hydrolysis of the trimethylsilyl esters serves to release the carboxylic acid. Amines may be recovered from O-methyl, O-ethyl, and O-benzyl carbamates after reaction with iodotrimethylsilane in chloroform or sulfolane at 50—60° and subsequent methanolysis. The conversion of dimethyl, diethyl, and ethylene acetals and ketals to the parent aldehydes and ketones under aprotic conditions has been accomplished with this reagent. The reactions of alcohols (or the corresponding trimethylsilyl ethers) and aldehydes with iodotrimethylsilane give alkyl iodides and a-iodosilyl ethers,respectively. lodomethyl methyl ether is obtained from cleavage of dimethoxymethane with iodotrimethylsilane. 

LLE is a widely used technique among the official US-EPA methods for the preconcentration of pesticides in liquid samples. Nonpolar solvents for the LLE of pesticides include w-hexane, benzene, and ethyl acetate. Water-miscible solvents for this purpose include dichloromethane, methanol, acetonitrile, acetone, and water, which have been employed for the extraction of residues from high-moisture commodities. Mixed solvents have often been used to finely adjust the solvent strength. Thus, various carbamate pesticides were extracted from aqueous environmental samples with chloroform and determined by HPLC with a mean recovery of 71 Also, a method based on the extraction by sonication of solid samples placed in small columns with a low volume of ethyl acetate was developed for the extraction of thiocarbamates and other herbicides from soil with recoveries between 89 and 109%. ... 

The popularity of the poly(saccharide) derivatives as chiral stationary phases is explained by the high success rate in resolving low molecular mass enantiomers. It has been estimated that more than 85% of all diversely structured enantiomers can be separated on poly(saccharide) chiral stationary phases, and of these, about 80% can be separated on just four stationary phases. These are cellulose tris(3,5-dimethylphenyl carbamate), cellulose tris(4-methylbenzoate), amylose tris(3,5-dimethylphenyl carbamate), and amylose tris(l-phenylethyl carbamate). Typically, n-hexane and propan-2-ol or ethanol mixtures are used as the mobile phase [111]. Both the type and concentration of aliphatic alcohols can affect enantioselectivity. Further mobile phase optimization is restricted to solvents compatible with the stationary phase, such as ethers and acetonitrile, as binary or ternary solvent mixtures, but generally not chloroform, dichloromethane, ethyl acetate, or tetrahydrofuran. Small volumes of acidic (e.g. tri-fluoroacetic acid) or basic (n-butylamine, diethylamine) additives may be added to the mobile phase to minimize band broadening and peak tailing [112]. These additives, however, may be difficult to remove from the column by solvent rinsing to restore it to its original condition. 

For the sake of increased stability and improved storage, somewhat less reactive alternatives have been prepared from the labile chloroformate. For example, 2-(trimethylsilyl)ethyl -succinimidyl carbonate has been used to prepare Teoc-protected amino acids in water or dioxane using sodium hydrogen carbonate or triethylamine as the base. - 2-(Trimethylsilyl)ethyl 4-nitrophenyl carbo-nate2 246 g commercially available reagent (mp 34-36 C) that reacts with amino acids in a mixture of aqueous sodium hydroxide and rert-butyl alcohol or dioxane. Simple amines can be acylated with triethylamine under anhydrous conditions [Scheme 8.105]. Teoc derivatives can also be prepared by an exchange reaction using an aryl carbamate derivative and 2-(trimethylsilyl)ethanol as shown in Scheme 8.106. ... 

The bis-(A,A -dimethylthiocarbamate) (10.0 g, 0.035 mol) was heated in the bulk at 260°C under nitrogen for 2 h. After cooling, the remaining material was crystallized from chloroform/methanol and further recrystallized from methyl ethyl ketone to afford 8.3 g bis-(A, A -dimethyl-5-carbamate), in a yield of 83%, m.p. 201-203°C. 

The reaction between ethyl Hthiopropiolate and the N-acylpyridinium salt formed by reaction of 4-methoxy-3-methyl-5-(triisopropylsilyl)pyridine 2363 with (+)-frafis-2-(a-cumyl)-cyclohexyl chloroformate (TCC chloro-formate) was the starting point in the synthesis of (-l-)-aUopumihotoxin 267A (1718) by Comins et al. (Scheme 301). The dihydropyridone product (—)- 2364 was obtained diastereoselectively (>96%) before hydrogenation to the saturated ester (+)-2365. However, some epimerization of the methyl substituent was apparent after cleavage of the TCC carbamate with lithium methoxide and cyclization to the indolizidinone (—)-2366 (dr 8 1). Acetoxylation at C-8 with lead tetraacetate was stereoselective, and introduced the acetate from the axial direction, possibly by stereoelec-tronicaUy-controUed intramolecular transfer of acetate from a lead—enol intermediate. The acetoxy product (—)-2367 was protodesilylated with formic acid, after which a one-pot tandem reduction with K-Selectride followed by hthium aluminum hydride gave diol (- -)-2368 with complete... 

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