Efficient Resolution of Menthylamine with Inexpensive ( R, R)- Tartaric Acid by Dielectrically Controlled Resolution (DCR)

A practical procedure for the resolution of menthylamine 2 with (R,R)-tartaric acid [(R,R)-3] as resolving agent is presented. Variation of the solvent system allows both enantiomers of 2 to be selectively crystallized. Performing the resolution in methanol containing 6% water leads to (-)-2(R,R)-3MeOH. The other, less-soluble diastereomeric salt is obtained by applying a solvent system consisting of methanol with 19% water with a yield of 14%. Subsequent basic workup with aqueous sodium hydroxide gave the free menthylamine compounds. Further workup of the mother liquors and an additional recrystallization step allowed the (-)-2 center dot(R,R)-3 center dot MeOH salt to be obtained in an overall yield of 22%; the other salt (+)-2 center dot(R,R)-3 center dot MeOH center dot H2O was obtained in 23% yield. This is another important example of the dielectrically controlled resolution of an interesting amine by using inexpensive (R,R)-tartaric acid as resolving agent.