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Synlett 2002(7): 1170-1172
DOI: 10.1055/s-2002-32577
LETTER
© Georg Thieme Verlag Stuttgart · New York

High Throughput Synthesis of Functionalised 1,3-Diones and Subsequent Heterocycle Formation

David A. Price*, Simon Gayton, Paul A. Stupple
Department of Discovery Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK
Fax: +44(1304)658422; e-Mail: david_a_price@sandwich.pfizer.com;
Further Information

Publication History

Received 22 May 2002
Publication Date:
07 February 2007 (online)

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Abstract

A functionalisation of 1,3-diones using hypervalent iodine has been developed that is useful in the preparation of libraries of heterocyclic compounds.

Key words

iodosylbenzene - alcohols - combinatorial chemistry - heterocycles - diones

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11

The reactions were conducted in 96 well plates and the experimental procedure for a representative sample was as follows: To a solution of 3-methylbenzyl alcohol (14 mg, 117 µmol) in chloroform (0.25 mL) was added 3,5-heptanedione (10 mg, 78 µmol) in chloroform (0.20 mL), boron trifluoride etherate (12 µl, 93µmol) and iodosyl-benzene (20 mg, 93 µmol). After being shaken for 12 h water (0.30 mL) was added and the plate shaken for a further
10 min. The aq layer was removed and hydrazine (5 µL,
117 µmol) added and the plate shaken for 12 h. The solvent was removed under reduced pressure and the residue purified by HPLC using a Phenomenex Luna C8 column eluted with trifluoroacetic acid in water(0.1% v/v): acetonitrile (95:5) (10 mL/min) to furnish 3,5-diethyl-1H-pyrazol-4-yl-3-methylbenzyl ether (5 mg, 28%); retention time 3.24 min; 1H NMR (500 MHz; CDCl3): δ = 7.26 (1 H, dd, J = 7.4, 7.4 Hz), 7.20 (1 H, s), 7.17 (1 H, d, J = 7.4 Hz), 7.15 (1 H, d, J = 7.4 Hz), 4.78 (2 H, s), 2.53 (4 H, q, J = 7.7 Hz), 2.37 (3 H, s), 1.21 (6 H, t, J = 7.7 Hz); LRMS: m/z = 245, MH+.