Trifluoroacetic acid → Ceftobiprole

Participants

Reaction Steps

5.2 (large scale): A suspension of 5.785 g of (6R,7R)-7-[(Z)-2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-trityloxyimino-acetylamino]-3-[(E)-(R)-1′-tert.-butoxycarbonyl-2-oxo-[1,3′]bipyrrolidinyl-3-ylidene-methyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid and 1.69 ml of triethylsilane in 25 ml of dichloromethane was treated at −15° with 7.21 ml of trifluoroacetic acid and the solution was heated to 30° for 30 min after which time HPLC indicated completion of the reaction. The mixture was evaporated to dryness, the residue was digested with 60 ml of ethyl acetate, the suspension was filtered and the residue dried to give 3.43 g of the crude title compound as a brown solid, containing about 1.4 equivalents of ethylacetate. 1H-NMR (d6-DMSO): 13.9 (s, br., 1H, COOH); 11.94 (s, 1H, OH); 9.50 (d, J=8.4, 1H, NH—C(7)); 8.96 (s, br., 2H, NH2); 8.07 (s, br., 2H, NH2); 7.26 (s, br., 1H, CH—C(3)); 5.88 (dd, J=8.4 and 4.9, 1H, H—C(7)); 5.18 (d, J=4.9, 1H, H—C(6)); 4.64 (m, 1H); 3.87 (s, br., 2H H2C(4)); 3.9-2.7 (m, 8H); 2.2-2.0 (m, 2H).

Provenance & Evidence