Phenyl dichlorophosphate synthesis

A practical synthesis of a-amido 3-lactams uses a Dane salt (9) formed by the reaction of a methan-olic solution of the potassium salt of glycine with methyl acetoacetate (Scheme 9). The salt (9) readily reacts with a Schiff base in the presence of triethylamine and e.g. a chloroformate ester. Other activating agents such as phenyl dichlorophosphate - or phosphorus oxychloride - have also been successfully used. 

The discovery synthesis of sofosbuvir (Scheme 3) employed the couphng reaction of PSI-6206 (10) and phosphoramidating reagent 46 which was prepared freshly from phenyl dichlorophosphate 45 and isopropyl L-alanate 44. This couphng resulted in a 1 1 mixture of diastereomers (1 and 28). From this mixture, sofosbuvir (1) was isolated either by HPLC or recrystallization. ... 

Setzer and co-workers repwrted the synthesis of 1,3,2-oxazaphospholane from the reaction between (lR,2R)-(-)-pseudoephedrine, phenyl dichlorophosphate and triethylamine in ethyl acetate. Triethylamine hydrochloride was filtered off and the solvent removed from the filtrate imder reduced pressure [66],... 

Esterification.—iVAWW -Tetramethylchloroformamidinium chloride, which is readily prepared from iVAWW -tetramethylurea and oxalyl chloride, is an efficient reagent for the esterification of carboxylic acids with alcohols yields of between 66 and 97% are obtained, and the method has also been applied to macrolide synthesis. A modified one-pot procedure for the esterification of carboxylic acids, using phenyl dichlorophosphate-dimethylformamide complex, has appeared. A simple method of activation of carboxylic acids, using methanesulphonyl chloride and triethylamine followed by addition of the alcohol and 4-dimethylaminopyridine, leads to esters in 57— 96% yield for thirteen examples. 0-Methylcaprolactim reacts with carboxylic acids to give methyl esters in 73—91 % yield for seven examples and 2-iodoethyl esters are prepared from acyl chlorides, ethylene oxide, and sodium iodide. Transesterification, catalysed by titanium(iv) alkoxides, provides an effective method for synthesis of esters. Diethyl trichloromethylphosphonate reacts with carboxylic acids to give ethyl esters via transesterification, in 52 to 98 % yield. ... 

---