Deprotection of N-tosylated indoles and related structures using cesium carbonate

Tetrahedron Letters

Volumn 47, Issue 36, 2006, Pages 6425-6427

  Bajwa, Joginder S ^a   Chen, Guang Pei ^a   Prasad, Kapa ^a   Repič, Oljan ^a   Blacklock, Thomas J ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Azaindoles; Cesium carbonate; Imidazoles; Indoles; N detosylation

Indexed keywords

CESIUM CARBONATE; CESIUM ION; INDOLE DERIVATIVE; METHANOL; TETRATHIAFULVALENE DERIVATIVE; TOLUENESULFONIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL STRUCTURE; DEPROTECTION REACTION; STRUCTURE ACTIVITY RELATION;

EID: 33746628876     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2006.06.132     Document Type: Article

References (16)

1. Fleming I., Frackenpohl J., and Ila H. J. Chem. Soc., Perkin Trans. 1 (1998) 1229-1235 and Ref. 8 cited there in
2. Green T.W., and Wuts P.G.M. Protective Groups in Organic Chemistry. 3rd ed. (2005), Wiley Interscience, New York
3. Kocieński P.J. Protective Groups. 3rd ed. (2003), Thieme, New York
4. Gilbert E.J., Chisholm J.D., and Van Vranken D.L. J. Org. Chem. 64 (1999) 5670-5676
5. Garg N.K., Sarpong R., and Stoltz B.M. J. Am. Chem. Soc. 124 (2002) 13179-13184
6. Sabitha G., Abraham S., Subba Reddy B.V., and Yadav J.S. Synlett 1 (1999) 1745-1746
7. Witulski B., and Alayrac C. Angew. Chem., Int. Ed. 41 (2002) 3281-3284
8. Nyasse B., Grehn L., and Ragnarsson U. Chem. Commun. (1997) 1017-1018
9. Muratake H., and Natsume M. Hetrocycles 29 (1989) 783-794
10. MacCoss R.N., Henry D.J., Brain C.T., and Ley S.V. Synlett (2004) 675-678
11. Haskins M.C., and Knight D.W. Tetrahedron Lett. 45 (2004) 599-601
12. 3H in the reaction mixture was confirmed by comparison of HPLC analysis of the reaction mixture with authentic samples. The formation of dimethyl ether was assumed on the basis of the corresponding reaction carried out in n-butanol where the formation of the dibutyl ether by-product was confirmed by GC-MS.
13. A representative procedure is as follows: N-Tosyl 5-bromoindole 9 (2.1 g, 6.0 mmol) was dissolved in a mixture of THF (50 mL) and MeOH (25 mL) at ambient temperature. Cesium carbonate (5.85 g, 18.0 mmol) was added to the clear solution. The resulting mixture was stirred at ambient temperature and the progress of the reaction was monitored by HPLC. When the reaction was complete (18 h), the mixture was evaporated under vacuum. To the residue was added water (25 mL) and the mixture was stirred at ambient temperature for 10 min. The solids were filtered, washed with water (15 mL) and dried at 45 °C/1.5 mbar/18 h to give crude product 10 (1.156 g, 98.3%). An analytically pure sample was obtained in 88.2% yield and 100% purity (HPLC) by recrystallization of crude product (1.156 g) from n-heptane (15 mL).
14. All N-tosyl derivatives were prepared by following the procedure described in. Poissonnet G., Théret-Bettiol M.-H., and Dodd R.H. J. Org. Chem. 61 (1996) 2273-2282
15. The pKa of indole is reported to be 20.95 according to:. Bordwell F.G. Acc. Chem. Res. 21 (1988) 456-463
16. The pKa's of azaindoles are reported to be 4.50-8.26 according to:. LeHyaric M., Vieira de Almeida M., and Nora de Souza M.V. Quim. Nova 25 (2002) 1165-1171