A general method is described for the preparation of N-unsubstituted azetidinones. The imine derived from p-anisidine and cinnamaldehyde is annelated with azidoacetic trifluoroacetic anhydride to yield the azetidinone 9. Treatment of 9 with ceric ammonium nitrate (CAN) yields the N-dearylated product 3. Similarly, treatment of the imine derived from p-anisidine and methyl glyoxylate methyl hemiacetal with N-phthalimidoacetyl chloride yields azetidinone 13. Derivatives of 13 at C-3 and C-4 when treated with 17, 19, and 21. Acylated derivatives of 3-aminomonobactamic acid (1) + 3 are efficacious antimicrobial agents for a variety of grampositive and negative bacteria.1 2345In particular, compound 2 (SQ 26 776) possesses a broad spectrum of gram-negative

The reaction of a variety of methyl esters with dimethylsulfoxonium methylide at 0-25 degrees C affords the chain-extended beta-keto dimethylsulfoxonium ylides. Subsequent treatment with hydrogen chloride in THF proceeds with loss of DMSO to afford the corresponding alpha-chloroketones. This sequence has been utilized to convert the methyl esters of CBZ-protected alanine and valine to the anti N-protected alpha-amino epoxides, which are important pharmaceutical intermediates. When the same protocol is applied to BOC-protected phenylalanine methyl ester, epimerization occurs so that the use of a more reactive aryl ester is required. This chemistry provides a practical route to alpha-chloroketones that avoids the use of toxic and explosive diazomethane.

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Development of an efficient and scalable process for the human immunodeficiency virus (HIV) protease inhibitor BMS-232632 1-[4-(pyridin-2-yl)phenyl]-5(S)-2,5-bis{[N-(methoxycarbonyl)-L-tert-leucinyl]-amino}-4(S)-hydroxy-6-phenyl-2-azahexane, is described. The key step in the synthesis of the intermediate N-1-(tert-butyloxycarbonyl)-N-2-[4-(pyridin-2-yl)benzylidene]hydrazone (11) was the Pd-mediated coupling of boronic acid 9 with 2-bromopyridine. An efficient procedure was developed for the chemoselective reduction of hydrazone 11 to hydrazine carbamate 4 (6) was prepared stereoselectively from chiral diol 10. The subsequent union of 4 and 6 followed by coupling with N-methoxycarbonyl-L-tert-leucine provided the free base BMS-232632 in high yield. Evaluation of a variety of salts and identification of bisulfate salt 19 with enhanced bioavailability are also described. . The key intermediate N-(tert-butyloxycarbonyl)-2(S)-amino-1-phenyl-3(R)-3,4-epoxy-butane