Ethoxymethyl ethyl ketone

In the laboratory of E.B. Pedersen, several 2-methylsulfanyl-1H-imidazoles were prepared and tested for their activity against HIV-1 These compounds can be regarded as novel non-nucleoside reverse transcriptase inhibitors. The required a-aminoketone hydrochloride building blocks were prepared using the Dakin-West reaction. L-Cyclohexylalanine was dissolved in excess pyridine and propionic anhydride and was kept at reflux overnight. The resulting a-propionylamino ethyl ketone was hydrolyzed with concentrated hydrochloric acid and the a-aminoketone hydrochloride was heated with one equivalent of potassium thiocyanate in water to afford 4-cyclohexylmethyl-5-ethyl-1,3-dihydroimidazole-2-thione. This material was then advanced to 4-cyclohexylmethyl-1-ethoxymethyl-5-ethyl-2-methylsulfanyl-IH-imidazole. 

Thiazole acid chlorides react with diazomethane to give the diazoketone. The later reacts with alcoholic hydrogen chloride to give chloroacetylthiazole (Scheme 16). However, the Wolff rearrangement of the diazoketone is not consistently satisfactory (82). Heated with alcohol in the presence of copper oxide the 5-diazomethylketone (24) gives ethyl 5-thiazoleacetate (25) instead of the expected ethoxymethyl 5-thiazolyl ketone (Scheme 17) (83). 

Fluoride-induced -elimination of p-(trimethylsily )ethyl ethers, which is the cornerstone of the 2-(trtmethylsilyl)ethoxymethyl (SEM) protecting group for hydroxyl functions (see section 4.4.5), has been modified for use in deprotecting cyclic acetals. For example, 4-(trimethylsilyl)methyM,3-dioxolanes46 and 5-tri-methylsilyl-13-dioxanes47 cleave on heating with lithium tetrafluoroborate [Scheme 2.16], The method works well for unhindered aldehydes and ketones. 

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