Amines benzyl chloroformate

Amino Acids. Chloroformates play a most important role for the protection of the amino group of amino acids (qv) during peptide synthesis (32). The protective carbamate formed by the reaction of benzyl chloroformate and amino acid (33) can be cleaved by hydrogenolysis to free the amine after the carboxyl group has reacted further. The selectivity of the amino groups toward chloroformates results in amino-protected amino acids with the other reactive groups unprotected (34,35). Methods for the preparation of protected amino acids on an industrial scale have been developed (36,37). A wide variety of chloroformates have been used that give various carbamates that are stable or cleaved under different conditions. 

A,r-Benzyl groups can be removed by reaction of amines with chloroformates. This can be a useful method for protecting-group manipulation if the resulting carbamate is also easily cleaved. A particularly effective reagent is a-chloroethyl chloroformate, which can be removed by subsequent solvolysis.78... 

A solution of the hydroxylamine (1.73 g, 3.7 mmol) in MeOH (50 mL) was treated with a 20% w/w aqueous solution of TiClj (1.43 g, 9.2 mmol, in 5.7 mL of HjO) at room temperature for 15 min, then 5-M aqueous NaOH was added, and stirring was continued for an additional 5 min. The mixture was extracted with ethyl acetate (4 x 25 mL), the combined extracts were washed with brine, dried (MgSO,, and concentrated to afford the crude amine, which was used in the next step without purification. To a cooled (0°C) and stirred mixture of the crude amine and 7% aqueous NaHCOj (20 mL) in 1,4-dioxane (50 mL) was added benzyl chloroformate (0.57 mL, 4.0 mmol). Stirring was continued at 0°C for 20 min, then H O (80 mL) and CHjClj (50 mL) were added. The organic layer was separated, and the aqueous layer was extracted with (2 x 25 mL). The... 

Try to anticipate the formation of azeotropes when distillation and concentration occur. Unexpected azeotropes may cause unsafe operations. For instance, distillative removal of water from the reaction of an amine with benzyl chloroformate (PhCH2COCl) resulted in formation of an azeotrope of water and benzyl chloride, a common impurity in benzyl chloroformate [40]. 

Tin(ll) chloride reduction of the azidotriflates 81 followed by intramolecular cycliza-tion with sodium acetate in methanol and subsequent protection of the resulting secondary amine with benzyl chloroformate afforded the a- and -furanoside carbamates 83 and 82. Hydrolysis of 82 and 83 by TEA in aqueous dioxane followed by sodium borohydride reduction of the resulting lactol furnished the protected 1-deoxynojirimcin 84 (49%). Subsequent hydrogenation of 84 afforded 2. 

A synthesis of the intermediate 71, as aprecursor to (-)-swainsonine (1), has been reported (Scheme 8). Prolonged hydrogenation of the azide 69, obtained from D-mannose in eight steps, in methanol and then in acetic acid afforded the pyrrolidine 70 in 90% yield. Protection of the secondary amine in 70 with benzyl chloroformate followed by sodium periodate oxidation and subsequent sodium borohydride reduction gave 71. 

BENZYL CHLOROFORMATE (501-53-1) Combustible liquid (flash point 176°F/80°C oc). Vigorous decomposition occurs at these temperatures thus, these values are anomalous due to the effect of the decomposition products (benzyl chloride and carbon dioxide). Reacts with water, producing hydrochloric acid. Violent reaction with strong oxidizers, bases. Incompatible with strong acids, nitrates. The aqueous solution is incompatible with sulfuric acid, alkalis, ammonia, aliphatic amines, alkanolamines, alkylene oxides, amides, epichlorohydrin, organic anhydrides, isocyanates, nitromethane, vinyl acetate. Attacks metals in the presence of moisture. 

Reaction of a primary amine with chloroform in the presence of an alkali hydroxide gives the isocyanide. This reaction has long been known for qualitative detection of primary amines but it often gives good yields on a preparative scale. It usually occurs exothermally on mere mixing of the components. By using benzene as solvent Malatesta637 achieved yields of 80-85% from some aliphatic and arylalkyl amines (butyl, isopentyl, pentyl, benzyl). 

Alkylation of the lithium enolate of 800 with 799 gives 801 as an inseparable 1 1 mixture of C-3 diastereomers. [2,3]-Sigmatropic rearrangement of 801 occurs upon treatment with MSH followed by triethyl phosphite. Protection of the newly formed amine is accomplished in situ with benzyl chloroformate in the presence of sodium bicarbonate. The rearrangement occurs with 85% chirality transfer and concomitant loss of the TMS protecting group. 

Removal of the methoxymethyl groups from 43 with HCl, followed by protection of the secondary amine with benzyl chloroformate afforded the carbamate 9. Selective silylation of the 4-hydroxy group of 9 by treatment with 1.2 equiv of tert-butyldimethylsilyl chloride and 2.4 equiv of imidazole in DMF at room temperature for 1 h afforded the corresponding silyl ether as a single isomer in 80% yield that was subjected to acetylation at the C-3 hydroxyl group to afford the carbamate 11, which upon removal of the Cbz and TBDMS groups furnished 1. 

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