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Process for preparation of Adamantane-1-methanol

IP.com Disclosure Number: IPCOM000238523D
Publication Date: 2014-Sep-03
Document File: 1 page(s) / 8K

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Process for preparation of Adamantane-1-methanol

    Adamantane-1-methanol can be prepared by reacting Adamantane-1-carboxylic acid (referred to as Compound-1) and alkyl chloroformate, followed by reduction ofthe obtained anhydride product using Sodium borohydride.

    The alkyl chloroformate can be, for example, isobutyl chloroformate, ethyl chloroformate, methyl chloroformate, isopropyl chloroformate.

    The obtained Adamantane-1-methanol can be used to prepare(1S,3S,5S)-2- [(2S)-2-amino-2-(3-hydroxy-1-adamantyl) acetyl]-2-azabicyclo[3.1.0]hexane-3- carbonitrile.

Procedure:

    10 gm Adamantane -1-carboxilic acid (Compound 1) was dissolved in 50 ml methyl tetrahydrofuran at room temperature under nitrogen atmosphere. N-methyl morpholine (8.41 gr) was added. The obtained clear solution was cooled to -10ºC and isobutyl chloroformate was slowly added at temperature of from about -10ºC to about - 5ºC. The reaction mass was stirred at -10ºC (for how long?) followed by additional stirring at at -5ºC for 1.5 hours. Water (50 ml) was added to the reaction mass at 5-10ºC and the mass was stirred. The layers were separated and the aqueous layer was extracted with methyl tetrahydrofuran. The organic layers were combined and cooled to -20ºC. Sodium borohydride solution (4.22 gms in 20 ml water) was added while maintaining a temperature up to 0ºC. The obtained suspension was stirred for 2 hours at -5 to 0ºC followed by quenching with acetic acid (5 ml). The layers were separate...