Amines 2- ethyl chloroformate

Nucleophilic aromatic substitution of the anion from ary lace ton itrile 113 on the dichloroni-trobenzene 114 results in replacement of the para halogen and formation of 115. Reduction of the nitro group gives the corresponding aniline (116). Acylation of the amine with 3,5-diiodoacetylsa-licylic acid 117 by means of the mixed anhydride formed by use of ethyl chloroformate, gives, after alkaline hydroly.sis, the anthelmintic agent closantel (118) [28]. 

Demethylation of the tricyclic antihistamine 9, with cyanogen bromide gives the secondary amine 10 acylation of that intermediate with ethyl chloroformate affords the nonsedating H-1 antihistaminic agent loratidine (11) [3], It is of interest that this compound does not contain the zwitterionic funcrion which is thought to prevent passage through the blood-brain barrier, characteristic of this class of compounds. 

Carbodiimides have been prepared by desulfurization of thioureas by metal oxides, by sodium hypochlorite,4 or by ethyl chloroformate in the presence of a tertiary amine by halogena-tion of ureas or thioureas followed by dehydrohalogenation of the N,N -disubstituted carbamic chloride 8 and by dehydration of disubstituted ureas using -toluenesulfonyl chloride and pyridine.7 The method described above is a modification of that of Campbell and Verbanc. ... 

The present method utilizes dichlorocarbene generated by the phase-transfer method of Makosza4 and Starks.5 The submitters have routinely realized yields of pure distilled isocyanides in excess of 40%.6 With less sterically hindered primary amines a 1 1 ratio of amine to chloroform gives satisfactory results. Furthermore, by modifying the procedure, methyl and ethyl isocyanides may be prepared directly from the corresponding aqueous amine solutions and bromoform.7 These results are summarized in Table I. 

In this series, too, replacement of the N-methyl by a group such as cyclopropylmethyl leads to a compound with reduced abuse potential by virtue of mixed agonist-antagonist action. To accomplish this, reduction of 24 followed by reaction with tertiary butylmagnesium chloride gives the tertiary carbinol 27. The N-methyl group is then removed by the classic von Braun procedure. Thus, reaction with cyanogen bromide leads to the N-cyano derivative (28) hydrolysis affords the secondary amine 29. (One of the more efficient demethylation procedures, such as reaction with ethyl chloroformate would presumably be used today.) Acylation with cyclopropylcarbonyl chloride then leads to the amide 30. Reduction with lithium aluminum hydride (31) followed by demethylation of the phenolic ether affords buprenorphine (32).9... 

Part 21 Determination of ethylenediamine and hexamethylenediamine in food simulants Derivitization of the free amine using ethyl chloroformate followed by GC with flame ionisation detection... 

Amine 17 (0.57 g, 2 mmol) was treated with rBuLi (4.7 mL, 1.5 m solution in pentane, 7 mmol). Ethyl chloroformate (0.32 g, 3 mmol) was added and the mixture was treated as described above. p-Toluenesulfonic acid (0.25 g,... 

One application in liquid chromatography which does alter the separation process is the use of a specific series of derivatives to enable the separation of chiral (optical isomers) forms of alcohols, amines and amino acids using reverse-phase separation. FLEC is available in the two chiral forms (+)-l-(9-fluorenyl) ethyl chloroformate and (—)-l-(9-fluorenyl) ethyl chlorofor-mate (Figure 3.12). Reaction of two stereoisomers of a test compound (e.g. T+ and T—) with a single isomer of the derivatizing reagent (e.g. R+) will result in the formation of two types of product, T+R+ and T—R+. It is possible to separate these two compounds by reverse-phase chromatography. 

Hydrophobic, fluorinated hyperbranched grafts were synthesized from an ethyl chloroformate activated hyperbranched 3-PAA/Au graft using the fluorinated alkyl amine H2N(CH2)(CF2)6CF3. Reaction of an activated 3-PAA/Au film with H2N(CH2 ) (CF2 leCFs produced a fluorinated film that almost doubled in thickness. XPS analysis showed 46 atom-% F in the product fluoramidated graft which is 86% of the theoretical atomic concentration for a homogenous... 

Reduction of a-imino ketones 52, prepared from 1,2-diketones 51 and 1 equiv of an amine, with sodium in ether, followed by treatment with ethyl chloroformate or... 

Cyclization of the product (27-2) under Friedel-Crafts conditions gives the desired indolinone (27-3). Reaction of the carbanion obtained on treatment of that with 3-chloropropyldimethylamine then gives the alkylation product (27-4). It should be noted that, in spite of this extra step, the scheme is greatly simplified by starting with the very readily available tertiary amine. The superfluous methyl group is then removed by reaction of (27-4) with ethyl chloroformate in the current version of the Von Braun reaction. There is thus obtained amedalin (27-5). Reduction of the amine by any of several methods, for example diborane, leads to the antidepressant daledalin (27-6) [28]. 

Reaction of ethyl chloroformate with amines to give ethyl alkylcarba-mates [28]. 

The carboxyl group of 4-oxo-4//-pyrimido[2,l-a]isoquinoline-3-carboxylic acids was esterified with various alcohols [84JAP(K)84/172490] and was converted into N-substituted 3-carboxamides by treatment with ethyl chloroformate in the presence of triethylamine in methylene chloride, followed by amines and hydroxylamine at 0°C [84JAP(K)84/172490 85EUP143001]. 

Benzothiazine-2,4-diones are synthesized by reacting 2-mercaptobenzoate esters firstly with ethyl chloroformate and then with an amine, or more directly by fusing the benzoate with urea. A third route is to treat the corresponding benzamide with phosgene (Scheme 99) <77ACH(92)317>. 

Reaction of 230 with ethyl chloroformate gave a mixture of ring-opened compounds that could be reduced with lithium aluminum hydride or catalytically (Scheme 30) the latter method provides a secondary amine (231) as the major product. 

The triethylamine salt of 2,2-dimethyl-3-(3,4-methylenedioxyphenyl)-propionic acid (5.4 g amine, 11.4 g acid) was dissolved in 10 mL 11,0 and diluted with sufficient acetone to maintain a clear solution at ice-bath temperature. A solution of 6.4 g ethyl chloroformate in 40 mL acetone was added to the 0 °C solution over the course of 30 min, followed by the addition of a solution of 4.1 g sodium azide in 30 mL H20. Stirring was continued for 45 min while the reaction returned to room temperature. The aqueous phase was extracted with 100 mL toluene which was washed once with H20 and then dried with anhy drou s Mg S04. Thi s org ani c sol uti on of the azide was heated on a steam bath until nitrogen evolution had ceased, which required about 30 min. The solvent was removed under vacuum and the residue was dissolved in 30 mL benzyl alcohol. This solution was heated on the steam bath overnight. Removal of the excess benzyl alcohol under vacuum left a residue 13.5 g of l-(N-(benzyloxycarbonyl)amino)-1,1 -dimethyl-2-(3,4-methylenedioxyphenyl)ethane as an amber oil. The dimethyl group showed, in the NMR, a sharp singlet at 1.30 ppm in CDCH,. Anal. (C19H2lN04) C,H. This carbamate was reduced to the primary amine (below) or to the methylamine (see under MDMP). 

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). 

The 1-phenyltetrahydroisoquinolines cryptostyline I (7) and cryptostyline II (8) have been synthesized by the condensation of 3,4-dimethoxyphenylethyl-amine with piperonal and veratric aldehyde respectively, followed by treatment with ethyl chloroformate and reduction with lithium aluminium hydride.21... 

To a solution of 4-amino-5-chloro-2-methoxybenzoic acid (20.2 g) in methyl isobutylketone (250 ml) and triethyl amine (15.3 ml) was slowly dropped ethyl chloroformate (9.6 ml). The reaction mixture was stirred for 30 min at room temperature. To the formed mixed anhydride was then added l-[3-(4-fluorophenoxy)-propyl]-3-methoxy-4-piperidinamine (28.2 g) and the reaction mixture was stirred for 2 hours at room temperature. Subsequently, the reaction mixture was washed with water (80 ml) and a NaOH solution (6.5% w/v, 50 ml). The organic layer was warmed to 65°C and methanol (50 ml) and water (8.5 ml) were added. The solution was cooled slowly and stirred for 2 days during which crystallisation occurred, yielding benzamide, 4-amino-5-chloro-N-(l-(3-(4-fluorophenoxy)propyl)-3-methoxy-4-piperidinyl)-2-methoxy-, monohydrate, cis- (Cisapride) having a cis/trans ratio higher than 99/1. 

---