Diisopropylethylamine → HCID 67674080, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 490.7 g (3.0 Mol) chloro-oxo-acetic acid tert-butyl ester (6) in 4.41 l methylene chloride was added 577 g (5.7 Mol) calcium chloride. The suspension was cooled to 0-5° C. A cold (0° C.) solution of 575 g (1.48 Mol) (2R, 3S)-[2-[4-(tert-butyl-dimethyl-silanyloxy)-3-oxo-butyl]-4-oxo-azetidin-3-yl]-carbamic acid tert-butyl ester (5) and 385 g (3.0 Mol) N,N-diisopropylethylamine was added at such a rate that the temperature does not rise above 5° C. (1.5 h). The reaction mixture was warmed to 23° C. and stirred for 1 h. The solids were removed by filtration and washed with 1.0 l methylene chloride. The combined filtrates were extracted with 1.5 l water, twice with 1.5 l sodium bicarbonate 5% and once again with 1.5 l water. The aqueous phases were extracted with 1.0 l methylene chloride. The combined organic phases were dried over 500 g sodium sulfate and filtered. The solids were washed with 1 l methylene chloride. The combined filtrates were concentrated to a volume of 5.0 l. To this solution 20 l n-hexane was added and the mixture was concentrated to a volume of 10 l. The product was allowed to crystallize while stirring at room temperature for 16 h. The precipitate was collected by filtration, washed with 4 l n-hexane and dried at 0.1 torr at 40° C. to yield 550 g of (2R, 3S)-{3-tert-butoxy carbonylamino-2-[4-(tert-butyl-dimethyl-silanyloxy)-3-oxo-butyl]-4-oxo-azetidin-1-yl}-oxo-acetic acid tert-butyl ester (7) as colorless crystals (69% Th.); m.p.: 102-103° C.

Provenance & Evidence