The present invention provides a method for preparing a pregabalin intermediate 3-carbamoymethyl-5-methylhexanoic acid without solvent. The method comprises the following steps: a) cooling an ammonia water system to a certain temperature; b) adding 3-isobutylglutaric anhydride dropwise to the system, then keeping temperature, and reacting; c) after completing the reaction, adding an acid to the system to adjust pH; d) after adjusting pH, cooling, then keeping temperature, crystallizing, then suction filtering and drying; and e) adding a solvent to the dried substance, slurrying, and suction filtering and drying to obtain the final product. The method provided in the present invention for preparing 3-carbamoymethyl-5-methylhexanoic acid is high-yield, green, environmentally-friendly, simple and convenient, and of less pollution.

The present invention provides a method for preparing a pregabalin intermediate 3-carbamoymethyl-5-methylhexanoic acid without solvent. The method comprises the following steps: a) cooling an ammonia water system to a certain temperature; b) adding 3-isobutylglutaric anhydride dropwise to the system, then keeping temperature, and reacting; c) after completing the reaction, adding an acid to the system to adjust pH; d) after adjusting pH, cooling, then keeping temperature, crystallizing, then suction filtering and drying; and e) adding a solvent to the dried substance, slurrying, and suction filtering and drying to obtain the final product. The method provided in the present invention for preparing 3-carbamoymethyl-5-methylhexanoic acid is high-yield, green, environmentally-friendly, simple and convenient, and of less pollution.

The present invention provides a process for preparing 2-methyl-N-(2′-methylbutyl)butanamide of the following formula (1): the process comprising: subjecting an α-arylethyl-2-methylbutylamine compound of the following general formula (2): wherein Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, to N-2-methylbutyrylation to form an N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound of the following general formula (3): wherein Ar is as defined above, and removing the α-arylethyl group of the resulting compound (3) to form 2-methyl-N-(2′-methylbutyl)butanamide (1).

##STR00001##

The present invention provides a process for preparing 2-methyl-N-(2′-methylbutyl)butanamide of the following formula (1): the process comprising: subjecting an α-arylethyl-2-methylbutylamine compound of the following general formula (2): wherein Ar represents a substituted or unsubstituted aryl group having 6 to 20 carbon atoms, to N-2-methylbutyrylation to form an N-α-arylethyl-2-methyl-N-(2′-methylbutyl)butanamide compound of the following general formula (3): wherein Ar is as defined above, and removing the α-arylethyl group of the resulting compound (3) to form 2-methyl-N-(2′-methylbutyl)butanamide (1).

##STR00001##

A mild and efficient synthesis of primary amines and amides from aldehydes or ketones using a heterogeneous metal catalyst and amine donor is disclosed. The initial heterogeneous metal-catalyzed reaction between the carbonyl and the amine donor components is followed by the addition of a suitable acylating agent component in one-pot, thus providing a catalytic one-pot three-component synthesis of amides. Integration of enzyme catalysis allows for eco-friendly one-pot co-catalytic synthesis of amides from aldehyde and ketone substrates, respectively. The process can be applied to asymmetric synthesis or to the co-catalytic one-pot three-component synthesis of capsaicin and its analogues from vanillin or vanillyl alcohol. A co-catalytic reductive amination/dynamic kinetic resolution (dkr) relay sequence for the asymmetric synthesis of optically active amides from ketones is disclosed. Implementation of a catalytic reductive amination/kinetic resolution (kr) relay sequence produces the corresponding optically active amide product and optical active primary amine product with the opposite stereochemistry from the starting ketones.

A mild and efficient synthesis of primary amines and amides from aldehydes or ketones using a heterogeneous metal catalyst and amine donor is disclosed. The initial heterogeneous metal-catalyzed reaction between the carbonyl and the amine donor components is followed by the addition of a suitable acylating agent component in one-pot, thus providing a catalytic one-pot three-component synthesis of amides. Integration of enzyme catalysis allows for eco-friendly one-pot co-catalytic synthesis of amides from aldehyde and ketone substrates, respectively. The process can be applied to asymmetric synthesis or to the co-catalytic one-pot three-component synthesis of capsaicin and its analogues from vanillin or vanillyl alcohol. A co-catalytic reductive amination/dynamic kinetic resolution (dkr) relay sequence for the asymmetric synthesis of optically active amides from ketones is disclosed. Implementation of a catalytic reductive amination/kinetic resolution (kr) relay sequence produces the corresponding optically active amide product and optical active primary amine product with the opposite stereochemistry from the starting ketones.

The present invention provides processes for the preparation of Tasimelteon (1), as well as processes for the preparation of intermediates of Formulas (2), (3) and (4) useful in the preparation of Tasimelteon (1).

##STR00001##

The present invention provides processes for the preparation of Tasimelteon (1), as well as processes for the preparation of intermediates of Formulas (2), (3) and (4) useful in the preparation of Tasimelteon (1).

##STR00001##

The present invention provides a scalable synthesis of enantiomerically pure brivaracetam, and related derivatives.

The present invention provides a scalable synthesis of enantiomerically pure brivaracetam, and related derivatives.