Dimethylformamide → Acyclovirvalericester

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A mixture of acyclovir prepared according to UK Patent No. 1523865 (3.11 moles), 4-dimethylaminopyridine (4.91 moles) and dimethylformamide (5.6 L) was stirred under nitrogen with heating on steam bath to give a homogeneous solution. On cooling to room temperature valeryl chloride (4.91 moles) was added dropwise while the temperature was maintained at 20°-25° C. Progress of the reaction was monitored by HPLC (Partisil ODS-3, methanol:water 50:50) and the reaction was terminated when the level of residual acyclovir was less than 0.5% (AUC). The mixture was cooled to 5° C., filtered and the cake was washed with dimethylformamide (200 ml). The combined filtrates were diluted with absolute ethanol (1 L), stirred for two hours at ambient temperature and concentrated to a thick oil. Methanol (16 L) was added and the resulting suspension was refluxed for 1.5 hours, cooled to 5° C. and filtered. The crude product was washed with methanol (200 mL) and dried under vacuum to constant weight to give 819 g (85.1% yield) of 9-(2-valeryloxyethoxymethyl) guanine, M.p. 215°-217° C.

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