1097616-52-8

Upstream product

• 675126-08-6 (1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride salt 
• 108-24-7 acetic anhydride 
• 1159007-68-7 N-((R)-4-(3,4-dichlorophenyl)-1,2-dihydronaphthalen-1-yl)acetamide 
• 1006692-60-9 N-((S)-1-(3,4-dichlorophenyl)-1,2-dihydronaphthalen-4-yl)acetamide 

Downstream Products

• 675126-08-6 (1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride salt 
• 1097616-55-1 2-((1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)isoindoline-1,3-dione 

Relevant academic research and scientific papers

ENAMIDE PROCESS

A convenient method for converting oximes into enamides is disclosed. The process produces enamides without the concomitant production of a large volume of metallic waste. The enamides are useful precursors to amides and amines.

A chemoenzymatic approach to enantiomerically pure amines using dynamic kinetic resolution: application to the synthesis of norsertraline

Racemization catalyst 5c and the enzyme Candida antarctica lipase B were combined in a one-pot dynamic kinetic resolution (DKR) of primary amines in which a wide range of amines were transformed to their corresponding amides in up to 95% isolated yield and > 99% ee. The DKR protocol was applicable with either isopropyl acetate or dibenzyl carbonate as the acyl donor. In the latter case, release of the free amine from the carbamate products was carried out under very mild conditions. The racemization of (S)-1-phenylethylamine with several different Ru catalysts was also evaluated. Catalyst 5c, of the Shvo type, was able to selectively racemize amines and was also compatible with the reaction conditions used for DKR. A racemization study of three different amines with varying electronic properties was also performed. Competitive racemization of a 1:1 mixture of the deuterated and non-deuterated amine was carried out with 5c and a primary kinetic isotope effect was observed for all three amines, providing support that the rate-determining step is β-hydride elimination. The chemoenzymatic DKR protocol was applied to the synthesis of norsertraline (16) by using a novel route starting from readily available 1,2,3,4-tetrahydro- 1-naphthy lamine (1o).

PREPARATION OF CHIRAL AMIDES AND AMINES

This invention provides a convenient method for converting oximes into enamides. The process does not require the use of metallic reagents. Accordingly, it produces the desired compounds without the concomitant production of a large volume of metallic waste. The enamides are useful precursors to amides and amines. The invention provides a process to convert a prochiral enamide into the corresponding chiral amide. In an exemplary process, a chiral amino center is introduced during hydrogenation through the use of a chiral hydrogenation catalyst. In selected embodiments, the invention provides methods of preparing amides and amines that include the 1,2,3,4-tetrahydro-N-alkyl-1-naphthalenamine or 1,2,3,4-tetrahydro-1-naphthalenamine substructure.