A novel process for preparing a stereospecific (S)-3-amino-1-substituted pyrrolidine used as a key intermediate in preparing quinolone and naphthyridone antibacterial agents where the 7-position is occupied with a sterospecific 3-aminopyrrolidine side chain is described starting from inexpensive L-aspartic acid. L-aspartic acid is converted to the desired (S)-3-aminopyrrolidine via a novel, high yield transformation of a substituted aziridine.
A test structure pattern includes a first comb having a first set of tines, and a second comb having a second set of tines of the same width and spacing as the first set of tines. When the test structure pattern is stepped between fields on a wafer, the first comb and the second comb at least partially overlap on photoresist over a scribe lane between the fields. When the photoresist is developed, the overlap of the first comb and the second comb generates a metal comb. Electrical continuity is checked for the metal tines of the metal comb to determine the misalignment of the fields.
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.