Trisodium citrate → Cefovecin sodium

Participants

Reaction Steps

Aluminium chloride (162 mg, 1.21 mmol) was added to anisole (7 ml) and dry dichloromethane (3.5 ml) at -20° C. and stirred for 15 min. The temperature of the cooling bath was then lowered to -40° C. before addition of a solution of 4-methoxybenzyl (6R,7R)-7-[2-(2-aminothiazol-4-yl)-2-(Z)-methoxyiminoacetamido]-3-[(S)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (235 mg, 0.41 mmol) in dichloromethane (5 ml). After 10 min., the solution was treated with trisodium citrate (0.5M, 12 ml) and then vigorously stirred for 10 min at room temperature. The aqueous phase was separated, washed with dichloromethane (×2) and concentrated in vacuo. The residue was chromatographed on HP20SS eluting with water, then 1% THF in water. Fractions containing the product, (h.p.l.c. analysis), were combined and freeze-dried to give the title compound (126 mg, 65%); νmax (KBr) 3401, 1761, 1669, 1603, 1533, 1040 cm-1 ; δH (d6 -DMSO, 250 MHz) 1.43-1.59 (1H, m), 1.71-1.88 (2H, m), 2.0-2.12 (1H, m), 3.18 and 3.37 (2H, ABq, J 17.4 Hz), 3.58 (1H, m), 3.78 (1H, m), 3.81 (3H, s), 4.87 (1H, dd, J 8.7, 6.7 Hz), 4.97 (1H, d, J 4.7 Hz), 5.50 (1H, dd, J 8.1, 4.7 Hz), 6.74 (1H, s), 7.21 (2H, br. s, exch.), 9.48 (1H, d, J 8.1 Hz, exch.). [Mass spectrum: +ve ion (thioglycerol) MH+ (476), MNa+ (498)].

Provenance & Evidence