Phosgene → Diisopropylamine

Participants

Reaction Steps

The 2-oxodioxolane ring can be prepared e.g. by the introduction of 1,2-dioxyethyl into 4-allyl-2-azetidinone (5a: Y=allyl) described in J. Chemical Society, Chem. Comm., 1979, 236 and carbonate formation according to the above reaction scheme. Namely, treatment of Compound (5a) with organosilyl reagent e.g. t-butyldimethylsilyl chloride, t-butyldiphenylsilylchloride, trimethylsilyl chloride, hexamethyldisilazane in an inert solvent e.g. dimethyl formamide, acetonitrile, hexamethylphosphorotriamide, dioxane, in the presence of an acid scavenger e.g. diiosopropylamine, triethylamine, pyridine, lutidine, at -20° C. to 25° C. for 0.5 to 24 hours to obtain 1-protected allyl compound (5b) and then treated with a base e.g. lithium diisopropylamide, sodium hydride, phenyllithium, butyl lithium, in an inert solvent e.g. dioxane, dimethoxyethane, tetrahydrofuran, at -80° C. to 0° C. for 1 to 5 hours to metalate to obtain 1-organosilyl-4-allyl-3-metalated-2-azetidinone (6). This is treated with 1,4-dioxaspiro[5,4]decan-2-one in an inert solvent e.g. ether, dimethoxyethane, tetrahydrofuran, at -80° C. to 0° C. for 1 to 3 hours to give a 1-organosilyl-4-allyl-3-hydroxyacetyl-2-azetidinone (7). This compound can be reduced with e.g. sodium borohydride, in alcohol at -80° C. to 10° C. for 0.5 to 5 hours to give 3-(1,2-dioxyethyl) compound (8; A=H) or alternatively, carbonyl addition reagent e.g. Grignard reagent, alkyl alkali metal, in an inert solvent e.g. dichloromethane, ether, tetrahydrofuran, at -20° C. to 100° C. for 0.5 to 5 hours or other conventional method to give the dihydroxyalkyl compounds (8; A≠H). The same compounds can be prepared by treatment of the said metalated azetidinone compounds (6) with protected hydroxyacetyl compound ACOCH2OZ in an inert solvent e.g. tetrahydrofuran at -80° C. to 0° C. for 0.1 to 5 hours to add Compound (6) to the carbonyl of ACOCH2OZ. The diol compound (8) is treated with carbonating reagent e.g. phosgene, phosgene dimer, pyrocarbonate ester, or the like in the presence of an acid scavenger e.g. diisopropylamine, triethylamine, pyridine, in an inert solvent e.g. dichloromethane, chloroform, benzene, ethyl acetate, in a conventional manner at -80° C. to 0° C. for 1 to 5 hours to give a 3-(2-oxo-1,3-dioxolanyl)-2-azetidinone compound (9).

Provenance & Evidence