Process for preparation of 2-chlorophenylglycine derivatives and enantiomerically separation
AssigneeRobert C. C. Wu
InventorsSimon Shin-Shing Lin, Cheng-Chung Chen
Life of this patent
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Abstract
The present invention relates to novel processes and intermediates for the preparation of R(−)-α-2-chlorophenylglycine, S(+)-α-2-chlorophenylglycine, and RS-2-chlorophenylglycine derivatives of formulas I, II and III, respectively. The resulting enantioseparative system was validated in order to evaluate the presence of the enantiomer in pharmaceutical samples. These compounds are found useful as an active ingredient for the pharmaceutical intermediate or as an active ingredient as the tools for delivery of drugs. 1
Claims13
Process for preparing the 2-chlorophenylglycine isomer of the compounds of formula
- 6
- characterized in that a (+)-camphor-10-sulfonic acid, a chiral ion-pairing reagent, was found to be an essential additive in obtaining a baseline separation and recycling from the mother liquid, thereof, the compounds of formula of 2-chlorophenylglycine isomer wherein steric isomers are R(−)-α-2-chlorophenylglycine (I) and S(+)-α-2-chlorophenylglycine (II).
- Wherein 2-chlorobenzaldehyde, ammonium hydrogencarbonate, and sodium cyanide in methanol and water was reacted.
Process for resolution of the enantiomeric isomer of the R(−)-α-2-chlorophenylglycine, S(+)-α-2-chlorophenylglycine from RS-2-chlorophenylglycine.
A racemic mixture of 2-chlorophenylglycine was prepared according to general synthetic procedures. The two enantiomers of 2-chlorophenylglycine were resolved by D-camphor sulfonic acid in water. A solution of racemic 2-chlorophenylglycine and D-camphor sulfonic acid in water, was stirred at 85° C. for 30 min. The precipitate S(+)CPG-DSC(S(+)-chlorophenylglycine-d-camphoric sulfonic acid) was filtered and washed with water. The filtrate was mother liquid as recycle. The wet S(+)CPG-DSC was dissolved in water and adjusted to pH 7. The precipitate was filtered and washed with water, dried to give S(+)-2-chlorophenylglycine. The filtrate was added to mother liquid and washed with 45% NaOH and concentrated and then added HCl to regenerate the target compound.
Enantiomeric isomer of the R(−)-α-2-chlorophenylglycine and S(+)-α-2-chlorophenylglycine and the racemic form of RS-2-chlorophenylglycine thereof.
A pharmaceutical composition for the synthesis of taxol, taxotere, clopidogrel, chlorfenapyr (Insecticide/Acaricide), AIDS and some antibiotics or a pharmaceutical acceptable material thereof, as an active ingredient in preparation for a pharmaceutically acceptable carrier or the active ingredient.
Dependencies are inferred from the claim text.