Process for the preparation of chiral 4-aryloxyazetidinones

A process for the preparation of the 4(S) enantiomer of a 4-aryloxyazetidin-2-one derivative of the formula I:

• ##STR8## wherein n is zero or a positive whole integer from 1 to 6;
• and
• X is selected from the group consisting of hydrogen, halogen, C.sub.1-6 alkyl and C.sub.1-6 alkoxy;
• which process comprises the following steps:
• (i) reaction of a compound of formula II:
• ##STR9## wherein R.sup.3 represents a hindered acyl residue, --CHR.sup.a R.sup.b, in which R.sup.a is selected from the group consisting of hydrogen, methyl and ethyl and R.sup.6 represents methyl or ethyl;
• with chlorosulphonyl isocyanate, to obtain a .beta.-lactam derivative of formula III:
• ##STR10## wherein R.sup.3 is as defined above, and the wavy line indicates that a mixture of enantiomers at the position indicated is obtained:
• (ii) reaction of the .beta.-lactam derivative of formula III with a phenolic compound of formula IV:
• ##STR11## wherein n and X are as defined above, and
• R.sup.4 represents a carboxy-protecting group;
• in the presence of a base, to obtain a compound of formula V:
• ##STR12## wherein n, R.sup.4, X and the wavy line are as defined above;
• (iii) removal of the carboxy-protecting group R.sup.4 from the compound of formula V thereby obtained, to obtain a compound of formula IA:
• ##STR13## wherein n, X and the wavy line are as defined above;
• (iv) treatment of the compound of formula IA thereby obtained with an approximately equimolar amount of a chiral amine, to obtain the corresponding chiral amine salt of the 4(S) enantiomer of the .beta.-lactam carboxylic acid of formula I;
• (v) filtering the reaction mixture;
• and
• (vi) acidifying the solid salt thereby obtained in order to regenerate the desired 4(S) enantiomer of the 4-aryloxyacetidin-2-one derivative of formula I in substantially optically-pure form.