合成路线1

7) The potassium salt (XIV), immediate precursor of sanfetrinem cilexetil can also be obtained as an enantiomeric mixture by the following sequence: The reduction of 2-oxocyclohexanecarboxylic acid ethyl ester (XXIX) with H2 over PtO2 in ethanol gives a mixture of the cis- and trans-2-hydroxycyclohexane (XXX), which is separated by distillation and treated with tert-butyldimethylsilyl chloride and imidazole in THF to yield cis-2-(tert-butyldimethylsilyloxy)cyclohexanecarboxylic acid ethyl ester (XXXI) as an enantiomeric mixture cis-(S,R)/cis-(R,S) (for the sake of clarity only one of the enantiomers is presented). The reduction of (XXXI) with diisobutylaluminum hydride (DIBAL) in ether affords the corresponding aldehyde (XXXII), which is treated with lithium trimethylsilylamide in THF to give the silylated imine (XXXIII). The cyclization of (XXXIII) with lithium tert-butyl acetate (XXXIV) in THF yields the silylated azetidinone (XXXV), which is deprotected by treatment with tetrabutylammonium fluoride (TBAF) in THF affording the hydroxyazetidinone (XXXVI). The reaction of (XXXVI) with 2,2-dimethoxypropane (XXXVII) and BF3 ethearate in dichloromethane gives the acetonide (XXXVIII), which is condensed with acetyltrimethylsilane (XXXIX) by means of lithium diisopropylamide (LDA) and potassium tert-butoxide (in order to introduce the 1-hydroxyethyl group) yielding the alkylated acetonide (XL). The trimethylsilyl protection of (XL) was removed and substituted with a more stable tert-butyldimethylsilyl (TBS) group affording (XLI), which is treated with pyridine chlorochromate (PCC) to give the previously reported 2-oxocyclohexylazetidinone (XVII) (Scheme 2), but as an enantiomeric mixture. The reaction sequence was continued (XVII) -> (XVIII) -> (XIX) -> (VIII) as in Scheme 2, and (VIII) -> (IX) -> (X) -> (XI) -> potassium salt (XIV) (all the compounds as enantiomeric mixtures). Note that if the starting compound is 2-oxocyclohexane-1(S)-carboxylic acid ethyl ester, instead of the racemic compound (XXIX), the potassium salt (XIV) can be obtained in enantiomerically pure form.