Hexamethylphosphoramide → Benzhydryl 7-(2-thienylacetamido)-3-(4-hydroxybutanoyloxymethyl)-2-cephem-4-carboxylate

Participants

Reaction Steps

To a solution of 2.24 g. (3.8 mmol) of benzhydryl 7-(2-thienylacetamido)-3-bromomethyl-3-cephem-4-carboxylate in 20 ml. of hexamethylphosphoramide (HMPA) at 0° C. under nitrogen was added a suspension of 0.530 g. (4.2 mmol) of sodium 4-hydroxybutanoate in 25 ml. of HMPA. After stirring 1.5 hours, ethyl acetate was added, and the resulting solution was washed with water (5X) and brine and dried over anhydrous MgSO4. Evaporation in vacuo to dryness provided 2.12 g. of product which was combined with that of an identical reaction ran on a 1 mmol scale. The combined products were chromatographed on a silica gel column using a cyclohexane:ethyl acetate (1:2) eluant to provide 293 mg. of a mixture of the title product and the corresponding 3-cephem compound. For the title product: nmr (CDCl3) δ1.7-2.6 ##STR26## 3.55 (m, 2, CH2OH), 3.83 (s, 2, side chain CH2), 4.63 (bs, 1, --CH2OH), 5.0 (s, 1, C4 --H), 5.23 (d, 1, J = 4 Hz, C6 --H), 5.58 (dd, 1, J = 4 and 8 Hz, C7 --H), 6.42 (bs, 1, C2 --H), 6.95 (s, 1, ester CH), and 7.36 (m, 13, thienyl + ArH).

Provenance & Evidence