The Vespiary

The Hive => Methods Discourse => Topic started by: Ezaey on December 21, 2003, 10:58:00 AM

Title: Questions about the synthesis of dextromethorphan
Post by: Ezaey on December 21, 2003, 10:58:00 AM

I have a few questions related to the synthesis of dextromethorphan. I've tried searching the site, but without satisfying results.

The only description of DXM's synthesis I've found is that of converting 1,2,3,4,5,6,7,8-octahydro-1-(4-methoxybenzyl)isoquinoline to the corresponding morphinan using Grewe's cyclization, but I have a couple of questions.

First of, does anyone know any other routes to dextromethorphan?

Second of, if one has racemethorphan, is it possible to separate the two isomers using l-tartaric acid? That would convert the levomethorphan into it's tartaric salt leaving the dextromethorphan in the solution, wouldn't it?

I apologize if my questions seem a bit "noobish", my knowledge about stereo chemistry is quite limited, but hey, at least I'm learning new things all the time. :D

Love!

Title: Synthesis of Dextromethorphan
Post by: Rhodium on December 21, 2003, 12:47:00 PM

Racemorphan stereoisomer separation into levo/dextro-methorphan with L-tartaric acid:

Patent US2676177 (http://l2.espacenet.com/dips/viewer?PN=US2676177&CY=gb&LG=en&DB=EPD)

Patent DE840242 (http://l2.espacenet.com/dips/viewer?PN=DE840242&CY=gb&LG=en&DB=EPD)

I have also found one stereoselective synthesis which does not produce the scheduled levo-isomer, but only dextromethorphan:

General asymmetric synthesis of benzomorphans and morphinans via enantioselective hydrogenation
M. Kitamura, Yi Hsiao and R. Noyori, H. Takaya
Tetrahedron Letters 28(41) , 4829-4832 (1987)
DOI:

10.1016/S0040-4039(00)96636-X (http://dx.doi.org/10.1016/S0040%2D4039%2800%2996636%2DX)

Abstract
A variety of optically active benzomorphans including metazocine and pentazocine as well as dextromethorphan, a morphinan, are obtainable by using the BINAP-ruthenium(II) catalyzed enantioselective hydrogenation as key operation.