Process for the enantioselective synthesis of hydroxypyrrolidine

Details Process for the enantioselective synthesis of hydroxypyrrolidine Process for the enantioselective synthesis of hydroxypyrrolidine

1997-01-23

1998-09-01

Powers, Fiona T.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

548237, 548239, 548544, C07D20712, C07D26314

Patent

active

058012478

ABSTRACT:
The present invention relates to processes for the enantioselective synthesis of hydroxypyrrolidines from amino acids. An amino methyl ester is used as the starting material. The ester is reacted with a benziminoethyl ether to produce an oxazoline or thiazoline. Specifically, L-serine methyl ester is used to produce 4-(carbomethoxy)-2-phenyl-.increment..sup.2 -oxazoline, and cysteine is used to produce the corresponding thiazoline. The oxazoline (or thiazoline) can be reduced to an aldehyde by treatment with a slight excess of DIBAL-H. The oxazoline is quenched with alcohol and reacted with (carbomethoxymethylene)triphenylphosphorane, to produce (S)-(+)-methyl (E)- and (S)-(-)-methyl (Z)-3-(4,5-dihydro-2-phenyl-4-oxazolyl)-2-propenoate. The double bond is hydroxylated to yield the diol esters. The resulting diol is then treated with aqueous acid to hydrolyze the oxazoline and recyclize to produce 3,4-dihydroxy-5-hydroxymethylpyrrolidone benzoate. This is treated with an excess of borane in tetrahydrofuran to yield (2-hydroxymethyl) 3,4-dihydroxypyrrolidine. The intermediate compounds are useful both in the present process and as final products themselves. The total yield of the mixture of isomers, as well as their ratio, can be varied.

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