A new industrial process for oxcarbazepine

被引：23

作者：

Fuenfschilling, PC ^{[1
]}

Zaugg, W ^{[1
]}

Beutler, U ^{[1
]}

Kaufmann, D ^{[1
]}

Lohse, O ^{[1
]}

Mutz, JP ^{[1
]}

Onken, U ^{[1
]}

Reber, JL ^{[1
]}

Shenton, D ^{[1
]}

机构：

[1] Novartis Pharma AG, CH-4002 Basel, Switzerland

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2005年 / 9卷 / 03期

关键词：

D O I：

10.1021/op049760a

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A novel industrial process for the antiepileptic drug oxcarbazepine I has been developed. Unlike the old process, the new process is free from halogenated solvents and can be performed in standard production equipment. It starts from commercially available 1,3-dihydro-1-phenyl-2H-indol-2-one 10. In the key step, an electrophilic ring closure reaction of 2-[(methoxycarbonyl)phenylamino] benzeneacetic acid 5 to 10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxylic acid methyl ester 6 in poly phosphoric acid was applied. For the manufacture of 5, a highly efficient process using a dianion strategy was developed.

引用

收藏

页码：272 / 277

页数：6

相关论文

共 12 条

[1] HETEROCYCLIC AROMATIC ANIONS WITH 4N+2-PI-ELECTRONS [J].

BORDWELL, FG ;

FRIED, HE .

JOURNAL OF ORGANIC CHEMISTRY, 1991, 56 (13) :4218-4223

[2] A NEW EFFICIENT AND MILD SYNTHESIS OF 2-OXINDOLES BY ONE-POT WOLFF-KISHNER LIKE REDUCTION OF ISATIN DERIVATIVES [J].

CRESTINI, C ;

SALADINO, R .

SYNTHETIC COMMUNICATIONS, 1994, 24 (20) :2835-2841

[3] PHOSPHORUS PENTOXIDE-METHANESULFONIC ACID - CONVENIENT ALTERNATIVE TO POLYPHOSPHORIC ACID [J].

EATON, PE ;

CARLSON, GR ;

LEE, JT .

JOURNAL OF ORGANIC CHEMISTRY, 1973, 38 (23) :4071-4073

[4] Copper catalyzed oxidation of tetralin to 1-(tert-butylperoxy)-tetralin by aqueous tert-butylhydroperoxide under phase transfer conditions. [J].

Feldberg, L ;

Sasson, Y .

TETRAHEDRON LETTERS, 1996, 37 (12) :2063-2066

[5] NEW SYNTHESIS OF 10-ALKOXY-5H-DIBENZ[B,F]AZEPINES [J].

HAASZ, F ;

GALAMB, V .

SYNTHETIC COMMUNICATIONS, 1994, 24 (05) :683-687

[6] Alkane oxidation with molecular oxygen using a new efficient catalytic system: N-hydroxyphthalimide (NHPI) combined with Co(acac)(n) (n=2 or 3) [J].

Ishii, Y ;

Iwahama, T ;

Sakaguchi, S ;

Nakayama, K ;

Nishiyama, Y .

JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (14) :4520-4526

[7] A new synthesis of oxcarbazepine using a Friedel-Crafts eyelization strategy [J].

Kaufmann, D ;

Fünfschilling, PC ;

Beutler, U ;

Hoehn, P ;

Lohse, O ;

Zaugg, W .

TETRAHEDRON LETTERS, 2004, 45 (27) :5275-5278

[8]

Kresge AJ, 1999, CAN J CHEM, V77, P1528

[9] New synthesis of oxcarbazepine via remote metalation of protected N-o-tolyl-anthranilamide derivatives [J].

Lohse, O ;

Beutler, U ;

Fünfschilling, P ;

Furet, P ;

France, J ;

Kaufmann, D ;

Penn, G ;

Zaugg, W .

TETRAHEDRON LETTERS, 2001, 42 (03) :385-389

[10]

Milanese A., 1996, WO Patent Application, Patent No. [9621649, 9,621,649]