Dichloromethane → Ceftobiprole

Temperature

30 °C

5.1 (small scale): A suspension of 149 mg 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 0.24 ml of methyl phenyl ether in 0.8 ml of formic acid was treated with 0.26 ml of dichloromethane containing 2% of trifluoroacetic acid and the solution was heated to 30° C. for 3 h after which time HPLC indicated completion of the reaction. The mixture was diluted with 3 ml of toluene and evaporated to dryness. The residue was diluted with 2 ml of methanol and 6 ml of water, the pH was adjusted to 9 by adding diluted ammonia and the aqueous layer was washed three times with ethyl acetate. The pH of the aqueous layer was adjusted to 3 by adding diluted hydrochloric acid and the solution was evaporated to dryness. The residue was digested with t-butyl methyl ether, filtered and the residue dried to give 73 mg of the NMR-pure title compound as a pale yellow solid. 1H-NMR (d6-DMSO+1 equivalent of CF3COOH, only some selected signals given): 7.26 (s, 1H, CH—C(3)); 5.88 (d, J=4.8, 1H, H—C(7)); 5.18 (d, J=4.8, 1H, H—C(6)); 3.88 and 3.86 (d each, J=18 each, 2H, CH2—S(5)); 3.5-2.8 (m, 8H, 4×CH2); 2.2-2.0 (m, 2H, CH2).

1. customcompletion of the reaction
2. customevaporated to dryness
3. additionThe residue was diluted with 2 ml of methanol and 6 ml of water
4. additionby adding diluted ammonia
5. washthe aqueous layer was washed three times with ethyl acetate
6. additionby adding diluted hydrochloric acid
7. customthe solution was evaporated to dryness
8. filtrationfiltered
9. customthe residue dried

ORD record

ord-4c2331eb421a4fceb37d30f2594d4e1c

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06504025B2