Disclosed herein are polymorphic and amorphous forms of anhydrate, hydrate, and solvates of (R)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide and methods of using such compositions for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging. Further disclosed are methods of making such polymorphic and amorphous forms.

The invention relates to methods of separating Trolox isomers (R)-Trolox and (S)-Trolox, comprising: (a) contacting a mixture of (R) and (S)-Trolox with a resolving agent selected from the group consisting of (1S,2S)-(+)-Pseudoephedrine, (R)-(+)-2-Amino-3-phenyl-1-propanol, (1R,2R)-(−)-Pseudoephedrine, and (S)-(−)-2-Amino-3-phenyl-1-propanol, wherein the resolving agent forms a solid salt with one of (R)-Trolox and (S)-Trolox, and substantially does not form a solid salt with the other; and (b) separating the solid salt from the Trolox isomer that did not form the solid salt with the resolving agent.

The invention relates to methods of separating Trolox isomers (R)-Trolox and (S)-Trolox, comprising: (a) contacting a mixture of (R) and (S)-Trolox with a resolving agent selected from the group consisting of (1S,2S)-(+)-Pseudoephedrine, (R)-(+)-2-Amino-3-phenyl-1-propanol, (1R,2R)-(−)-Pseudoephedrine, and (S)-(−)-2-Amino-3-phenyl-1-propanol, wherein the resolving agent forms a solid salt with one of (R)-Trolox and (S)-Trolox, and substantially does not form a solid salt with the other; and (b) separating the solid salt from the Trolox isomer that did not form the solid salt with the resolving agent.

Provided herein are methods of preparing a desired enantiomer 6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl) methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone, otherwise known as tipifarnib.

The present invention relates to a process for resolution of Chlocyphos of Formula (I) to obtain corresponding (S)- or (R)-isomers. The present invention further relates to a process of obtaining (S)-Chlocyphos using (R)-(+)-α-methylbenzylamine and (R)-Chlocyphos using (S)-α-methylbenzylamine. The said resolution process provides the corresponding isomer with chiral purity more than 98%.

##STR00001##

The present invention relates to a process for resolution of Chlocyphos of Formula (I) to obtain corresponding (S)- or (R)-isomers. The present invention further relates to a process of obtaining (S)-Chlocyphos using (R)-(+)-α-methylbenzylamine and (R)-Chlocyphos using (S)-α-methylbenzylamine. The said resolution process provides the corresponding isomer with chiral purity more than 98%.

##STR00001##

Provided is a method for producing an optically active substance, the method including an asymmetric induction, wherein an asymmetry inducer is allowed to act on a chiral molecule having a half-life of enantiomeric excess of shorter than 10 hours, thereby increasing abundance of one enantiomer of the chiral molecule. According to this method, one enantiomer of a chiral molecule that is susceptible to racemization can be selectively and efficiently obtained.

Provided is a method for producing an optically active substance, the method including an asymmetric induction, wherein an asymmetry inducer is allowed to act on a chiral molecule having a half-life of enantiomeric excess of shorter than 10 hours, thereby increasing abundance of one enantiomer of the chiral molecule. According to this method, one enantiomer of a chiral molecule that is susceptible to racemization can be selectively and efficiently obtained.

Described are processes for the manufacture of compounds containing a (S)-4,5-dihydro-1H-pyrazole ring. These processes include a chiral resolution step of an intermediate using selected chiral resolving agents. For example, the chiral resolving agents may be selected from (−)-quinine, (R)-phenethylamine, (S)-phenethylamine, (S)-1-naphthylethy lamine, (R)-(−)-2-amino-3-methyl-1-butanol, (−)-cinchonidine, (−)-spartein, (R)-1-naphthylethy lamine, D-arginine, L-lysine, (S)-(+)-2-pyrrolidinemethanol and(1R,2S)-(+)-cis-1-amino-2-indanol.

##STR00001##

The present invention provides a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Adopting a particular isomerization-crystallization condition makes it possible to a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Additionally, an intermediate efficacious for producing lacosamide is provided.