Methanesulfonic s. a. Mesyl

Metathesis s. Interchange Methane derivatives s. Diarylmethanes Methanesulfonic acid esters (s. a. Mesylation)... 

A cost effective and easily scaled-up process has been developed for the synthesis of (S)-3-[2- (methylsulfonyl)oxy ethoxy]-4-(triphenylmethoxy)-1 -butanol methanesulfonate, a key intermediate used in the synthesis of a protein kinase C inhibitor drug through a combination of hetero-Diels-Alder and biocatalytic reactions. The Diels-Alder reaction between ethyl glyoxylate and butadiene was used to make racemic 2-ethoxycarbonyl-3,6-dihydro-2H-pyran. Treatment of the racemic ester with Bacillus lentus protease resulted in the selective hydrolysis of the (R)-enantiomer and yielded (S)-2-ethoxycarbonyl-3,6-dihydro-2H-pyran in excellent optical purity, which was reduced to (S)-3,6-dihydro-2H-pyran-2-yl methanol. Tritylation of this alcohol, followed by reductive ozonolysis and mesylation afforded the product in 10-15% overall yield with excellent optical and chemical purity. Details of the process development work done on each step are given. 

N KOH and water added to crude 2,4-dichlorophenol- C, ice-cooled to 0 , mesyl diloride added dropwise with stirring from a hypodermic syringe, after 5 min. stirring more KOH-soln. and mesyl chloride added, again stirred 5 min., a third portion of KOH-soln. added, and allowed to react 15-30 min. -> 2,4-didilorophenyl-i C methanesulfonate. Y 87%. Also ss-labeling with mesyl- S diloride s. W.B. Burton and D. W. Stoutamire, Microchem. J. 18, 51 (1973). 

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