1- chloroethyl ethyl chloroformate

The unsymmetric 6-nitro-2,3-dihydro-l,4-ethanoquinoxaline (549, R = N02) and ethyl chloroformate naturally gave a mixture of ethyl 4-(2-chloro-ethyl)-7-nitro- (551) and ethyl 4-(2-chloroethyl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinecarboxylate (552) (CHCI3, 20°C, 1 h 30% each, after... 

The value of this new route immediately was recognized because 1-chloroethyl ethyl carbonate which could be obtained from 1-chloroethyl chloroformate and ethanol already was on the market as an alkylating agent to prepare the orally active antibiotic Bacampicillin . 

The sodium salt of diethyl -(ethoxycarbonyl)methylphosphonate reacts wth 2-chloroethyl chloroformate in THF at room Icmperature to produce the diethyl -ethoxycarbony -( ,3-dioxo an-2-ylidene)methylphosphonate in 57% yield. The same reaction conducted with ethyl chloroformate in CgHg or THF proceeds with the formation of a complex reaction mixture. By contrast, when the ethoxymagnesium salt is employed, the diethyl l,l-bz. v(ethoxycarbonyl)mclhy I phosphonate is isolated in 67% yield. The diethyl l-lithio-l-fluoro-l-(ethoxycarbonyl)methylphosphonate generated with n-BuLi in THF reacts with ethyl chloroformate to give only the diethyl l-fluoro-1,1-Z A(ethoxycarbonyl)methylphosphonate. ... 

The large-scale synthesis of a-chloroethyl chloroformate (ACE-Q) by the above method (stirring acetaldehyde with 1.1 equiv. of neat pho ene for 1 h in the presence of 3.0% benzyl tri-n-butylammonium chloride (BTBAC), giving an isolated yield of 96%) has a particular value since its ethanolysis product, a-chloroethyl ethyl carbonate, is a commercial alkylating agent used to mask carboxyls in penicillins and cephalosporins. 

Preparation of 4-( -Chloroethyl)-3,3-Diphenyl-1Ethyl-2-Pyrrolidinone A solution of a,a -diphenyl-a -(1-ethyl-3-pyrrolidyl)-acetonitrile in 70% sulfuric acid was heated at 130°-140°C for 48 hours, poured onto ice, made basic with sodium hydroxide, and extracted with chloroform. The chloroform solution was acidified with hydrogen chloride gas, dried over sodium sulfate and concentrated. The residue was refluxed in 500 ml of thionyl chloride for 3 hours the resulting solution was concentrated in vacuo and the residue was crystallized from isopropyl ether. 

A solution of 6-acetylcodeine (10.0 g, 29.3 mmol), 1-chloroethyl chloroformate (5.51 g, 37.8 mmol), and proton sponge (1.0 g) in methylene chloride (80 ml) was heated at reflux for 80 min. The reaction mixture was evaporated in vacuo to dryness. The residue was chromatographed on silica gel with ethyl acetate to give 6-acetyl-17-(l-chloroethoxycarbonyl)norcodeine as an oil (12.13 g), which was dissolved in methanol with a few drops of cone. HCI. The solution was heated at reflux for 1 hr and evaporated in vacuo to almost dryness. The residue was added hexane and filtered to give 6-acetylnorcodeine hydrochloride (10.7 g, 100% yield). 

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