The formal synthesis of chiral etodolac using chiral 1,2- di(alkylcarbonyl)oxypentan-3-one as chiral building block

Heterocycles

Volumn 51, Issue 7, 1999, Pages 1527-1541

  Chou, Shan Yen ^a   Tseng, Chin Lu ^a   Chen, Shyh Fong ^a  

^a Molecular Biology Division Devmt Center for Biotechnology   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

(1,8 DIETHYL 1,3,4,9 TETRAHYDROPYRANOL[3,4B]INDOL 1 YL) 1 ETHANOL; 1,2 DI(ALKYLCARBONYL)OXYPENTAN 3 ONE; ETODOLAC; UNCLASSIFIED DRUG;

ARACHIDONIC ACID METABOLISM; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CATALYSIS; CHIRALITY; CYCLIZATION; DIASTEREOISOMER; DRUG SYNTHESIS; DRUG TRANSFORMATION; ENANTIOMER; ENZYME SYNTHESIS; PROTON NUCLEAR MAGNETIC RESONANCE; RECEPTOR AFFINITY; STEREOCHEMISTRY;

EID: 0033166010     PISSN: 03855414     EISSN: None     Source Type: Journal    
DOI: 10.3987/COM-98-8456     Document Type: Article

References (22)

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4. The active (+)-etodolac has been assigned an S absolute configuration on the basis of a crystallographic analysis of the (S)-(-)-borneol ester of (-)-etodolac, see: L. G. Humber, C. A. Demerson, P. Swaminathan, and P. H. Bird, J. Med. Chem., 1986, 29, 871.
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8. Each chiral β-keto esters was prepared by esterification of 3-ketovaleric acid with L-borneol, L-menthol, and (-)-isopinocamphenol respectively using DCC.
9. 2 or toluene) was employed for this step, see: C. C. Shaw and K. Pelz, Eur. Pat. Appl., 1989, 306,149 (Chem. Abstr., 1989, 111, 174074).
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12. 2, δ 2.08 (m, 2H) in (±)-etodolac.
13. Another batch of experiments was carried out for optimization the yield of 18 (see EXPREIMENTAL).
14. 4/THF) of (±)-etodolac.
15. Although compound (20) might also be an optically active compound, its specific rotation data were not collected.
16. Similarly, a 1,2-migration with concomitant nucleophilic ethoxylation and ring constraction of chloroindoleins have been observed, see: M. E. Kuehne, D. M. Roland, and R. Hafter, J. Org. Chem., 1978, 43, 3705.
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19. K. Maruoka, T. Ooi, S. Nagahara, and H. Yamamoto, Tetrahedron, 1991, 47, 6983.
20. An irritant formalin odor was detected from the crude product.
21. 7
22. Since the polarities of 11 and 6 are very close, the purification step is skipped. No analytical data of 11 are collected, although the subsequent hydrolysis gives the corresponding diol (13) with satisfactory spectral data.