4-Methylmorpholine → (6R)-3-(azidomethyl)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Participants

Reaction Steps

The 3-aminomethylcephalosporin may be prepared as follows:-Oxalyl chloride (337 μl.) and DMF (330 μl.) were added to CH2Cl2 (20 ml.) at -10°, and stirred for 30 minutes. 2((Z)-t-Butoxycarbonylmethoxyimino)-2-(2 tritylaminothiazol-4-yl)acetic acid and N-methylmorpholine (510 μl.) were added and stirring continued for 30 minutes. Meanwhile in a separate flask, a suspension of 7-amino-3-azidomethylceph-3-em-4-carboxylic acid (987 mg.) in dichloromethane (8 ml.) was treated with N,O-bis(trimethylsilyl)acetamide (1.91 ml.), and stirred for 1 hour to give a clear solution, which was transferred by syringe to the acid chloride solution. After stirring the mixture for 1 hour at -10°, the temperature was allowed to rise to ambient. The mixture was poured into water (25 ml.) and organics extracted with EtOAc (3×25 ml.). The crude product was filtered through a short SiO2 column in EtOAc/HOAc 99:1 v/v, and evaporated to give 3-azidomethyl-7-[2-((Z)-t-butoxycarbonylmethoxyimino)-2-(2-tritylaminothiazol-4-yl)acetamido]ceph-3-em-4-carboxylic acid, having the following n.m.r. in solvent A:-1.4(s, 9H); 3.35(d, 1H); 3.63(d, 1H); 3.86(d, 1H); 4.38(d, 1H); 4.49(s, 2H); 5.09(d, 1H); 5.7(d, 1H); 6.73(s, 1H); 7.29(m, 15H).

Provenance & Evidence