An efficient asymmetric synthesis of a potent COX-2 inhibitor L-784,512

Tetrahedron Letters

Volumn 39, Issue 23, 1998, Pages 3961-3964

  Tan, Lushi ^a   Chen, Cheng Yi ^a   Larsen, Robert D ^a   Verhoeven, Thomas R ^a   Reider, Paul J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOOXYGENASE 2 INHIBITOR; L 784512; MEMBRANE PROTEIN; PROSTAGLANDIN SYNTHASE; UNCLASSIFIED DRUG;

ANTIINFLAMMATORY ACTIVITY; ARACHIDONIC ACID METABOLISM; ARTICLE; ENANTIOMER; ENZYME ACTIVITY; HYDROXYLATION; METHYLATION; NEPHROTOXICITY; REACTION ANALYSIS; STOMACH LESION;

EID: 0032482530     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)00735-7     Document Type: Article

References (12)

1. 1 Otto, J. C.; Smith, W. L. J. Lipid. Mediat. Cell Signal. 1995, 12, 139.
2. 2 Vane, J. R. Proc. Natl. Acad. Sci. USA 1994, 91, 2046.
3. 3 Laneuville, O. J. Pharmacol. Exp. Ther. 1994, 271, 927.
4. 4 Seibert, K. Proc. Natl. Sci. USA 1994, 91, 12013.
5. 5 Belley, M. Y.; Leblanc, J.Y.; Gauthier, E.; Grimm, M.; Therien, C. B.; Prasit, P.; Lau, C. K.; Roy, P. World Patent Application, WO 9714691.
6. 6 All new compounds were completely characterized by appropriate spectroscopic methods. All gave satisfactory elemental analyses.
7. 7 Duan, J.-X., Su, D.-B., Chen, Q.-Y. J. Fluorine Chem. 1993, 61, 279.
8. 8 (a) Procedure for the preparation of 3b from 4b: To a solution of 4b (11.30 g) and diisopropylethylamine (21 mL) in DMF (50 mL) was added dropwise chlorodifluoroacetic anhydride (11 mL) with an external cooling bath. Potassium fluoride (3.5 g) and cuprous iodide (9.5 g) were added after 5 min. The mixture was heated at 90 °C for 1 h, poured into 100 g of ice, extracted with ethyl acetate (2 x 100 mL), and concentrated. The residue was transferred into a funnel containing ∼ 250 g of silica get and eluted with 15% ethyl acetate in hexane. Concentration of the eluent gave 10.3 g (74%) of 3b as a white solid,
9. (b) Trifluoromethylation of allylic alcohols with methyl chlorodifluoroacetate has been reported. See, Duan, J.-X., Chen, Q.-Y. J. Chem. Soc. Perkin Trans 1, 1994, 6, 725.
10. 9 Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483.
11. 10 Experimentally, crude 10b (10.5 g, 82% ee) was dissolved in hot IPAc (90 mL) and then cooled to 23 °C. The crystal (12% ee, 14.3% recovery) was collected by filtration. The filtrate was diluted with hexane (final ratio of IPAc/hexane: 4/5) and the crystal was collected by filtration to give pure 10b (>98% ee, 72.4% recovery).
12. 11 Compound 2 was prepared in 72% yield by heating a mixture of 3,4-difluorophenol and bromoacetic acid in THF in the presence of 2 N NaOH.