Succinic anhydride → 5'-O-(3-Carboxy-1-oxopropyl)-2'-deoxy-2',2'-difluorocytidine

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Reaction Steps

A 600 mg portion of dry 2'-deoxy-2',2'-difluorocytidine, hydrochloride, was added to 6 ml of dry pyridine, and 804 mg of succinic anhydride was added. The reaction mixture was stirred at ambient temperature for 1.5 hours. The mixture was then concentrated to an oil under vacuum, and the oil was stored overnight in the freezer. It was then allowed to stand at ambient temperature for 4 hours, and was chromatographed over a 500 ml Q-Sepharose column (Pharmacia Inc.). The oil was dissolved in 6 ml of 0.lM ammonium acetate buffer, and was passed over the column, eluting with a gradient buffer which changed from 0.lM to 1.0M ammonium acetate, at pH 8.0 at all times. Analytical chromatography of the mixture on a small mono-Q column showed that bisacylated and tris-acylated products were present, as well as mono-acylated product and a small amount of starting material. The product-containing fractions, amounting to about 200 ml, were placed in a 37° C. bath, for 68 hours. At the end of that time, the tris-acylated product had been decomposed and both mono- and bisacylated products were still present.

Provenance & Evidence