| abstract |
The present invention provided a process for manufacture of amantadine nitrate derivatives, and the process comprises using adamantane as the raw material to prepare amantadine nitrate derivatives via the following steps: (1) synthesis of adamantanol; (2) carboxylation of adamantanol; (3) acetylation of adamantanoic acid; (4) reduction; (5) hydrolysis of amido adamantanol and Boc protection of amino group; (6) crystallization of Boc protected amantadinol; (7) nitrate esterification of Boc protected amantadinol; (8) refining of the product of nitrate esterification; (9) Boc deprotection and salt formation; and (10) refining of amantadine nitrate hydrochloride. The amantadine nitrate derivatives have the struction of:wherein, R<sub>1</sub> and R<sub>2</sub> are each independently hydrogen, straight-chain or branched-chain alkyl, or substituted or unsubstituted aryl or heteroaryl. The process of this invention is efficient, cost effective, environmentally friendly, safe, reliable, and suitable for industrial production. |