5-BENZYL 3-METHYL 1-(P-FLUOROPHENYL)-4-ISOPROPYL-1H-PYRAZOLE-3,5-DICARBOXYLATE synthesis

Yield:887703-73-3 65%

Reaction Conditions:

with ammonium cerium(IV) nitrate in tetrahydrofuran;water at 0; for 1 h;

Steps:

1.D; 1a (d) Step D. Preparation of 1-(4-fluoro-phenyl)-4-isopropyl-1 H-pyrazole-3.5-dicarboxylic acid 5-benzyl ester 3-methyl ester

To a solution of 1-(4-fluoro-phenyl)-4-isopropyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylic acid 5-benzyl ester 3-methyl ester (29.3, 73.5 mmol) in THF:Water (1:1, 500 mL) at 0° C. was slowly added ceric ammonium nitrate (80.5 g, 147 mmol; commercially available from Sigma Aldrich). The reaction was stirred at 0° C. for 1 hr after which time the THF was removed under reduced pressure and DCM (500 mL) was added. The organic layer was separated and washed with water and brine. The organic layer was dried over Na₂SO₄ and concentrated, and the product was purified by silica gel chromatography (5-15% EtOAc/Hex) to provide 1-(4-fluoro-phenyl)-4-isopropyl-1 H-pyrazole-3,5-dicarboxylic acid 5-benzyl ester 3-methyl ester (18.95 g, 65%):: H-NMR (CDCl₃) δ 7.29-7.21 (m, 5 H), 7.07 (d, 2 H), 6.94 (t, 2 H), 5.12 (s, 2 H), 3.89 (s, 3 H), 3.88-3.80 (m, 1 H), 1.31 (d, 6 H).

References:

US2006/111422,2006,A1 Location in patent:Page/Page column 18-19; 31