Claims
- 1. A process for enhancing the optical purity of the R-amino alcohol of formula: ##STR42## comprising the steps of: (a) adding slowly an acid solution or gas to a solution of the amino alcohol in an organic solvent to form a slurry of the acid addition salt of the amino alcohol;
- (b) concentrating the slurry of the amino alcohol acid addition salt of the amino alcohol;
- (c) flushing the concentrated slurry of the amino alcohol acid addition salt with organic solvent to adjust the solvent composition;
- (d) aging the slurry of the amino alcohol acid addition salt at ambient temperature for about 2 hours to about 24 hours;
- (e) filtering the aged slurry of the amino alcohol acid addition salt to isolate a wetcake of the amino alcohol acid addition salt;
- (f) washing the wetcake of the amino alcohol acid addition salt with cold organic solvent; and
- (g) drying the wetcake of the amino alcohol acid addition salt to isolate the amino alcohol acid addition salt as a solid with enhanced optical purity.
- 2. The process for enhancing the optical purity of the R-amino alcohol as recited in claim 1, wherein the acid has a pKa of less than or equal to 3.
- 3. The process for enhancing the optical purity of the R-amino alcohol as recited in claim 2, wherein the organic solvent is selected from the group consisting of: isopropyl acetate, ethyl acetate, toluene, methyl t-butyl ether, acetonitrile, tetrahydrofuran, methanol, ethanol, isopropanol, hydrocarbon solvents, and mixtures therefrom.
- 4. The process for enhancing the optical purity of the R-amino alcohol as recited in claim 3, wherein the acid has a pKa of less than or equal to 1.
- 5. The process for enhancing the optical purity of the R-amino alcohol as recited in claim 4, wherein the organic solvent is selected from the group consisting of: isopropyl acetate, ethyl acetate, toluene, methyl t-butyl ether, acetonitrile, tetrahydrofuran, methanol, ethanol, isopropanol, hydrocarbon solvent, and mixtures therefrom.
- 6. The process for enhancing the optical purity of the R-amino alcohol as recited in claim 5, wherein the acid is selected from the group consisting of: HX, where X is defined as halide (Cl, Br, I, or F), H.sub.2 SO.sub.4, trifluoroacetic acid, trichloroacetic acid, RSO.sub.3 H, where R represents (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl, (C.sub.2 -C.sub.6)-alkynyl, aryl which is defined as phenyl or naphthyl and heteroaryl which is defined as 5 or 6-membered ring substituted with one or two heteroatoms selected from O, S, N, and (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl, (C.sub.2 -C.sub.6)-alkynyl, aryl or heteroaryl can be substituted or unsubstituted with one, two or three substituents selected from the group consisting of: Br, Cl, F, I, (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl, (C.sub.2 -C.sub.6)-alkynyl, (C.sub.1 -C.sub.6)-alkoxy, cyano, nitro, hydroxy, CHO, CO.sub.2 H, SO.sub.3 H, COC.sub.1 -C.sub.6 -alkyl, CO.sub.2 C.sub.1 -C.sub.6 -alkyl, CONR.sup.1 R.sup.2, NR.sup.1 R.sup.2, NR.sup.1 COC.sub.1 -C.sub.6 -alkyl, wherein R.sup.1 and R.sup.2 are independently defined as: halo (Cl, Br, F, I), CF.sub.3, CN, NO.sub.2, NH.sub.2, NH(C.sub.1 -C.sub.6 -alkyl), N(C.sub.1 -C.sub.6 -alkyl).sub.2, CONH.sub.2, CONH(C.sub.1 -C.sub.6 -alkyl), CON(C.sub.1 -C.sub.6 -alkyl).sub.2, NHCONH.sub.2, NHCONH(C.sub.1 -C.sub.6 -alkyl), NHCON(C.sub.1 -C.sub.6 -alkyl).sub.2, CO.sub.2 -C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, C.sub.3 -C.sub.7 -cycloalkyl, or C.sub.1 -C.sub.6 -alkoxy, such that C.sub.1 -C.sub.6 -alkyl is unsubstituted or substituted with aryl, aryl is defined as phenyl or naphthyl, unsubstituted or substituted with C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkoxy, NO.sub.2, or halo (Cl, Br, F, I).
- 7. The process for enhancing the optical purity of the R-amino alcohol as recited in claim 6, wherein the organic solvent is selected from the group consisting of: isopropyl acetate, ethyl acetate, toluene, methyl t-butyl ether, acetonitrile, tetrahydrofuran, methanol, ethanol, isopropanol, and hydrocarbon solvents, and mixtures therefrom.
- 8. The process for enhancing the optical purity of the R-amino alcohol as recited in claim 7, wherein the acid solution or gas is selected from the group consisting of: 1,5 naphthalenedisulfonic acid, p-toluenesulfonic acid, CH.sub.3 SO.sub.3 H, triflic acid, and camphorsulfonic acid HCl, HBr, and H.sub.2 SO.sub.4.
- 9. The process for enhancing the optical purity of the R-amino alcohol as recited in claim 8, wherein the acid solution or gas and organic solvent are: HCl and isopropyl acetate, HBr and isopropyl acetate or HBr and a toluene-tetrahydrofuran mixture.
Parent Case Info
This application claims benefit of Provisional Appl. 60/057,891 filed Sep. 3, 1997 and Provisional Appl. 60/096,529 filed Aug. 14, 1998.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
3497517 |
Ettingen et al. |
Feb 1970 |
|
4085138 |
Whitney |
Apr 1978 |
|
5679857 |
Hijiya et al. |
Oct 1997 |
|
Foreign Referenced Citations (1)
Number |
Date |
Country |
0 582 455 A1 |
Mar 1993 |
EPX |
Non-Patent Literature Citations (1)
Entry |
Ryoichiro, N., et al., Chem. Abstract, Abstract No. 127:95076, 1997. |