Regioselective Hydroxylation of 2,4-Lutidine: A Practical Synthesis of 4-Hydroxymethyl-2-methylpyridine

John A. Ragan; Brian P. Jones; Clifford N. Meltz; John J. Teixeira

doi:10.1055/s-2002-20960

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Synthesis 2002(4): 0483-0486
DOI: 10.1055/s-2002-20960

PAPER

Regioselective Hydroxylation of 2,4-Lutidine: A Practical Synthesis of 4-Hydroxymethyl-2-methylpyridine

John A. Ragan*, Brian P. Jones, Clifford N. Meltz, Jr. John J. Teixeira
Chemical Research and Development, Pfizer Global Research & Development, P.O. Box 8156-101, Groton, CT 06340, Canada
Fax: +1(860)4416334; e-Mail: john_a_ragan@groton.pfizer.com;

Further Information

Publication History

Received 13 November 2001
Publication Date:
28 July 2004 (online)

Abstract
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Abstract

A practical synthesis of 4-hydroxymethyl-2-methylpyridine has been developed which makes use of Evans’ regioselective lithiation of readily available 2,4-lutidine and trapping with dimethylformamide.

Key words

lithiation - hydroxylation - regioselectivity - pyridines

References

1a Furukawa S. Pharm. Bull. (Japan) 1955, 3: 413 ; Chem. Abstr. 1955, 50, 13926

Google Scholar
1b Katz RB. Mistry J. Mitchell MB. Synth. Commun. 1989, 19: 317

Google Scholar
2 Evans DA. Cee VJ. Smith TE. Santiago KJ. Org. Lett. 1999, 1: 87

Crossref Google Scholar
3 Davis FA. Sheppard AC. Tetrahedron 1989, 54: 5703

Google Scholar
4a Thayer HI. Corson BB. J. Am. Chem. Soc. 1948, 70: 2330

Google Scholar
4b Gleich E. Warnke Z. Szafranek J. Malinski E. Phosphorus Sulfur 1986, 28: 315

Google Scholar
5a Jahangir Wang J. Smith RW. MacLean DB. Holland HL. Can. J. Chem. 1990, 68: 587

Google Scholar
5b Johnston KM. Williams GH. J. Chem. Soc. 1960, 1168

Google Scholar
6 Kaiser EM. Tetrahedron 1983, 39: 2055

Crossref Google Scholar
7 Wright ME. Yamada LY. Synth. Commun. 1988, 18: 1449

Google Scholar
8 Lehn J.-M. Ziessel R. Helv. Chim. Acta 1988, 71: 1511

Crossref Google Scholar
9a Sun L. Berglund H. Davydov R. Norrby T. Hammarstroem L. Korall P. Borje A. Philouze C. Berg K. Tran A. Andersson M. Stenhagen G. Mortensson J. Almgren M. Styring S. Akermark B. J. Am. Chem. Soc. 1997, 119: 6996

Crossref Google Scholar
9b Ito Y. Kobayashi K. Saegusa T. J. Organomet. Chem. 1986, 303: 301

Crossref Google Scholar
9c Elliott CM. Freitag RA. Blaney DD. J. Am. Chem. Soc. 1985, 107: 4647

Crossref Google Scholar
10 Trapping of a lithiated 4-methylpyridine with TMSCl is precedented in a related system: Fraser CL. Anastasi NR. Lamba JJS. J. Org. Chem. 1997, 62: 9314

Crossref Google Scholar
11 Andrews IP. Lewis NJ. McKillop A. Wells AS. Heterocycles 1996, 43: 1151

Google Scholar
12 Fleming I. Sanderson PEJ. Tetrahedron Lett. 1987, 32: 4229

Google Scholar
13 Ishihara T. Miwatashi S. Kuroboshi M. Utimoto K. Tetrahedron Lett. 1991, 36: 1069

Google Scholar
14a Vetelino JG. Coe JW. Tetrahedron Lett. 1994, 35: 219

Article in Thieme Connect Google Scholar
14b Dupau P. Renouard T. Le Bozec H. Tetrahedron Lett. 1996, 37: 7503

Article in Thieme Connect Google Scholar
14c Feliu L. Ajana W. Alvarez M. Joule JA. Tetrahedron 1997, 53: 4511

Article in Thieme Connect Google Scholar
14d Niu C. Li J. Doyle TW. Chen S.-H. Tetrahedron 1998, 54: 6311

Article in Thieme Connect Google Scholar
14e Sasaki I. Daran JC. Balavoine GGA. Synthesis 1999, 815

Article in Thieme Connect Google Scholar
15a Henze HR. Knowles MB. J. Org. Chem. 1954, 19: 1127

Google Scholar
15b Mathes W. Sauermilch W. Chem. Ber. 1960, 93: 286

Google Scholar
15c Mathes W. Sauermilch W. Chem. Ber. 1951, 84: 648

Google Scholar
15d Krasavin IA. Radin YP. Ryabokokylko YS. Parusnikov BV. Dziomko VM. Chem. Heterocycl. Compd. (Engl. Transl.) 1978, 14: 235

Google Scholar