Abstract: A method for producing substantially pure levorphanol and related compounds, when compared to the conventional process, is provided. In particular, a method for producing substantially pure levorphanol tartrate dihydrate is described. Also described are compositions comprising levorphanol and related compounds, particularly compositions comprising levorphanol tartrate dihydrate, levomethorphan, and norlevorphanol in which the levomethorphan and norlevorphanol are present in the composition in reduced levels.

Abstract: An improved lyophilized cyclophosphamide solid composition is described. The lyophilized cyclophosphamide solid composition is thermally stable, contains anhydrous cyclophosphamide and mannitol, and is substantially free of cyclophosphamide monohydrate. A method for preparing the lyophilized cyclophosphamide solid composition is also provided.

Abstract: An improved lyophilized cyclophosphamide solid composition is described. The lyophilized cyclophosphamide solid composition is thermally stable, contains anhydrous cyclophosphamide and mannitol, and is substantially free of cyclophosphamide monohydrate. A method for preparing the lyophilized cyclophosphamide solid composition is also provided.

Abstract: Novel methods and systems for producing a substantially pure d-threo stereoisomer of methylphenidate or a salt thereof are provided. In particular, methods and systems for producing d-threo-methylphenidate hydrochloride in pure stereoisomeric form from d-threo-ritalinic acid hydrochloride using diazomethane are described. The described methods can be performed on a large scale, and thus provide d-threo methylphenidate or a salt thereof, and particularly the hydrochloride salt of d-threo-methylphenidate, in stereoisomerically pure form and in large quantities from a single batch reaction. Also described are novel compositions of d-threo methylphenidate hydrochloride.

Abstract: Novel methods and systems for producing a substantially pure d-threo stereoisomer of methylphenidate or a salt thereof are provided. In particular, methods and systems for producing d-threo-methylphenidate hydrochloride in pure stereoisomeric form from d-threo-ritalinic acid hydrochloride using diazomethane are described. The described methods can be performed on a large scale, and thus provide d-threo methylphenidate or a salt thereof, and particularly the hydrochloride salt of d-threo-methylphenidate, in stereoisomerically pure form and in large quantities from a single batch reaction. Also described are novel compositions of d-threo methylphenidate hydrochloride.

Abstract: Novel methods and systems for producing a substantially pure d-threo stereoisomer of methylphenidate or a salt thereof are provided. In particular, methods and systems for producing d-threo-methylphenidate hydrochloride in pure stereoisomeric form from d-threo-ritalinic acid hydrochloride using diazomethane are described. The described methods can be performed on a large scale, and thus provide d-threo methylphenidate or a salt thereof, and particularly the hydrochloride salt of d-threo-methylphenidate, in stereoisomerically pure form and in large quantities from a single batch reaction. Also described are novel compositions of d-threo methylphenidate hydrochloride.

Abstract: Compounds and methods for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds from an isomerically pure starting material are described. In particular, methods of preparing a 3-(1-(dimethylamino)-2-methylpentane-3-yl)phenol as a substantially optically pure (R,R) stereoisomer are described. Using a method of the present invention, only the (R,R) and (S,S) stereoisomers of the target compound are produced, increasing the yield and stereoselectivity of the desired (R,R) stereoisomer.

Abstract: A method for releasing an anhydrous gas in a gas phase at a target rate includes the step of obtaining a vessel at least partially filled with the anhydrous gas. The anhydrous gas is at least partially in a liquid phase and the vessel has an outlet for releasing the anhydrous gas in the gas phase. The method further includes releasing at least a portion of the anhydrous gas from the vessel through the outlet in the gas phase; applying a heat transfer fluid having a temperature of 32° F. to 150° F. to an exterior surface of the vessel during the releasing step, such that the anhydrous gas in the liquid phase is evaporated and the anhydrous gas in the gas phase is released at the target rate; and measuring starting and end weights of the vessel to monitor the releasing of the anhydrous gas in the gas phase.

Abstract: The present invention provides a new process for the preparation of 2R,3S-N-isobutyl-N-(2-hydroxy-3-amino-4-phenylbutyl)-p-nitrobenzenesulfonylamide hydrochloride, wherein this compound is prepared directly from the chloromethylalcohol. Importantly, the process of the present invention results in higher yields of 2R,3S-N-isobutyl-N-(2-hydroxy-3-amino-4-phenylbutyl)-p-nitrobenzenesulfonylamide hydrochloride without sacrificing its purity. The processes of the present invention can be used to prepare not only the 2R,3S-derivative, but also the 2S,3S-, 2S,2R- and the 2R,3R-derivatives.

Abstract: A novel stereochemical mixture of 1,6-diaryl-2,5-diaminohexanes, such as a mixture of stereoisomers of 1,6-diphenylhexane-2,5-diamine, is described. Also described are methods of preparing stereochemically pure 1,6-diaryl-2,5-diaminohexanes, and particularly stereochemically pure 1,6-diphenyl-2,5-diaminohexane. Also described is the use of both the mixture of stereoisomers and the individual stereoisomers.

Abstract: Product yields in chemical reactions that produce a solid product from a liquid reaction mixture are improved by chromatographically separating certain key impurities from the product mixture prior to crystallization, or from the filtrate after crystallization in which case further product is crystallized from the filtrate. The removal of key impurities either before the first crystallization or between the first and second crystallizations facilitates the crystallization of product to produce a higher yield of product.

Abstract: The present invention provides compounds and methods that can be used to convert 1,2,4-triazole-3-carboxamides to the corresponding 3-cyano-1,2,4-triazoles reliably in one step, with high yields and without the need for elaborate purification.

Abstract: The present invention provides compounds and methods that can be used to convert the intermediate halomethyl ketones (HMKs), e.g., chloromethyl ketones, to the corresponding S,S- and R,S-diastereomers. More particularly, the present invention provides: (1) reduction methods; (2) inversion methods; and (3) methods involving the epoxidation of alkenes. Using the various methods of the present invention, the R,S-epoxide and the intermediary compounds can be prepared reliably, in high yields and in high purity.

Abstract: Product yields in chemical reactions that produce a solid product from a liquid reaction mixture are improved by chromatographically separating certain key impurities from the product mixture prior to crystallization, or from the filtrate after crystallization in which case further product is crystallized from the filtrate. The removal of key impurities either before the first crystallization or between the first and second crystallizations facilitates the crystallization of product to produce a higher yield of product.

Abstract: R-?-Lipoic acid and its homologs are converted to their magnesium salts in the presence of a reduced form of the acid, dihydro-(+)-lipoic acid in the case of R-?-lipoic acid itself. The reduced form serves as a polymerization inhibitor, resulting in a Mg di-R-?-lipoate product of higher purity. The reduced acid retained in the product tends to convert to the starting acid, thereby avoiding the inclusion of an extraneous polymerization inhibitor in the product.

Abstract: High yields and purity are obtained in the purification of enantiomers of chiral carboxylic acids by preparative-scale chromatography by including a tertiary alcohol in the mobile phase in conjunction with an acidic modifier and a hydrophobic solvent. The tertiary alcohol is superior to other, more commonly used alcohols by reducing the extent of esterification of the enantiomer that otherwise lowers the yield and the purity.

Abstract: R-?-Lipoic acid and its homologs are converted to their magnesium salts in the presence of a reduced form of the acid, dihydro-(+)-lipoic acid in the case of R-?-lipoic acid itself. The reduced form serves as a polymerization inhibitor, resulting in a Mg di-R-?-lipoate product of higher purity. The reduced acid retained in the product tends to convert to the starting acid, thereby avoiding the inclusion of an extraneous polymerization inhibitor in the product.

Abstract: The present invention provides a new process for the preparation of 2R,3S-N-isobutyl-N-(2-hydroxy-3-amino-4-phenylbutyl)-p-nitrobenzenesulfonylamide hydrochloride, wherein this compound is prepared directly from the chloromethylalcohol. Importantly, the process of the present invention results in higher yields of 2R,35-N-isobutyl-N-(2-hydroxy-3-amino-4-phenylbutyl)-p-nitrobenzenesulfonylamide hydrochloride without sacrificing its purity. The processes of the present invention can be used to prepare not only the 2R,3S-derivative, but also the 2S,3S-, 2S,2R- and the 2R,3R-derivatives.

Abstract: The present invention provides a new process for the preparation of 2R,3S-N-isobutyl-N-(2-hydroxy-3-amino-4-phenylbuty1)-p-nitrobenzenesulfonylamide hydrochloride, wherein this compound is prepared directly from the chloromethylalcohol. Importantly, the process of the present invention results in higher yields of 2R,3S-N-isobutyl-N-(2-hydroxy-3-amino-4-phenylbutyl)-p-nitrobenzenesulfonylamide hydrochloride without sacrificing its purity. The processes of the present invention can be used to prepare not only the 2R,3S-derivative, but also the 2S,3S-, 2S,2R- and the 2R,3R-derivatives.

Abstract: The present invention provides compounds and methods that can be used to convert nitrogen-containing-heteroaryl carboxamides to the corresponding nitrogen-containing-heteroaryl nitriles reliably in one step, with high yields and without the need for elaborate purification.