Process for the preparation of (2S)-tetrahydro-2.alpha.-methyl-6-oxo-4.beta..alpha.-carboxylic acid
AssigneeMerck & Co., Inc.
InventorsRaymond J. Cvetovich, David G. Melillo, Kenneth M. Ryan, Meyer Sletzinger
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Abstract
Disclosed is a process for preparing (2S)-tetrahydro-2.alpha.-methyl-6-oxo-4.beta.-amino-2H-pyran-3.alpha.-carb oxylic acid (I) which is useful in the synthesis of thienamycin. The process proceeds via a stereospecific reduction of the 2-acetyl-3-(R)-.alpha.-methylbenzylamino-2-pentenedioic acid diester (II). ##STR1## wherein R is, .alpha.-methylbenzyl, and R.sup.1 is lower alkyl having 1-6 carbon atoms or arylalkyl such as benzyl.
Claims2
A stereoselective reductive process for preparing ##STR26## comprising reaction of ##STR27## with 1-100 atmospheres pressure hydrogen gas, in the presence of a catalytic amount of PtO.sub.2, Pd/C, Pt/C, or Raney nickel;
- in a solvent which is isopropyl alcohol, methanol, ether, ethyl acetate or toluene;
- at a temperature of 0.degree.-85.degree. C. for from 2-72 hours;
- and in the presence of an activating Lewis acid which is BF.sub.3.OEt.sub.2, FeCl.sub.3 or AlCl.sub.3 ;
- wherein R.sup.1 is alkyl having 1-6 carbon atoms or benzyl;
- and R is (R)-.alpha.-methyl benzyl or (S)-.alpha.-methylbenzyl or lower alkyl esters of (R)- and (S)-.alpha.-carboxybenzyl or benzyl esters of (R)-and (S)-.alpha.-carboxy-benzyl.
Dependencies are inferred from the claim text.