Triethylamine → 4-Benzyloxy-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

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Reaction Steps

To a solution of 4-benzyloxy-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (77b) (6.98 g, 23.40 mmol) in CH2Cl2 (100 mL) was added thionyl chloride (2.04 mL, 28.1 mmol), followed by 10 drops of DMF. The mixture was refluxed for 2 h, then concentrated and dried under vacuum. The residue was dissolved in CH2Cl2 (100 mL), and 3-amino-1-methyl-pyrazole (2.73 g, 28.1 mmol) was added at 0° C., followed by triethylamine (6.52 ml, 46.80 mmol). The mixture was stirred at 0° C. to room temperature for 1 hr. The reaction was quenched with H2O, extracted with 3×CH2Cl2. The combined organic layers were dried over Na2SO4, concentrated and purified by flash column chromatography with 1-3% MeOH in CHCl3 to give a white solid (5.31 g, 60% yield). 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1 H) 7.29-7.50 (m, 6 H) 7.09 (d, J=1.01 Hz, 1 H) 6.84 (dd, J=8.08, 1.77 Hz, 2 H) 5.14 (s, 2 H) 3.83 (s, 3 H) 2.95-3.06 (m, 2 H) 1.50 (s, 6 H); LCMS for C22H23N3O3 m/z 378.20 (M+H+).

Provenance & Evidence