Sodium Iodide → 5'-Deoxy-5'-iodo-5-fluorouridine

Participants

Reaction Conditions

Reaction Steps

To a solution of 39.2 g (0.13 m) of 2′,3′-O-isopropylidene-5-fluorouridine in 55 ml of methylene chloride and 159 ml (1.98 m) of pyridine, cooled to +5° C., 60 g (0.315 m) of p-toluenesulfonyl chloride are added. The mixture thus obtained is stirred for 5 hours observing the formation of a plentiful precipitate. Then 160 ml of methylene chloride and 160 ml of water are added thereinto, whereby the temperature rises to 40° C. The phases are separated and the organic one is extracted with about 900 ml of N HCl; then the organic phase is washed with 2×100 ml of water. The organic phase, containing 0.117 m of 2′,3′-O-isopropylidene-5′-O-(p-toluenesulfonyl)-5-fluorouridine (yield —90% of the theoretical), is concentrated under vacuum until an oily residue is obtained, which is taken up with 2×100 ml of acetone. The oily residue is dissolved with 600 ml of acetone and 105 g (0.70 m) of sodium iodide are added to the solution. The mixture is heated for 5 hours at reflux, then cooled, concentrated under vacuum and the residue thus obtained is taken up with 2×80 ml of ethyl acetate. The residual oil is treated with 800 ml of ethyl acetate and 100 ml of water. The phases are separated and the aqueous one is treated with 2×80 ml of ethyl acetate. The collected organic phases are washed with 2×100 ml of a 5% aqueous solution of sodium metabisulphite, then with 100 ml of water. The organic phase, containing 0.113 m of 5′-deoxy-5′-iodo-2′,3′-0-isopropylidene-5-fluoro uridine (yield —97% of the theoretical), is concentrated under vacuum to a small volume; to the residue 560 ml of 80% aqueous acetic acid are added and the mixture is heated to 95° C. After 4-hour heating, a check by HPLC is performed (0.34% of residual starting product) After cooling, the mixture is concentrated under vacuum until an oily residue is obtained, which is taken up with 150 ml of ethyl acetate. The mixture is let to stand at 20÷25° C. for 15 ore. The product is filtered, washed with ethyl acetate and dried under vacuum at 45° C. Thus, 44.5 g of 5′-deoxy-5′-iodo-5-fluorouridine are obtained. M.p.=174÷175° C., purity (HPLC)=99.74% and [α]D=÷8.96° C. (c=1, CH3OH). The mother liquors are concentrate under vacuum and the residue is taken up with 50 ml of ethyl acetate; after 15 hours at +5° C., a further amount of 3.3 g of product are obtained. Total yield. 83% of the theoretical.

Provenance & Evidence