2,6-Difluorobenzaldehyde → 1-Isopropylsulfonyl-2-amino-6-(2-(2,6-difluorophenyl)-5-(phenyl)-oxazol-4-yl)-benzimidazole

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Reaction Conditions

Reaction Steps

To a solution of 1-isopropylsulfonyl-2-amino-6-(α-((tert-butyldimethylsilyl)oxy)-α-(phenyl)acetyl)-benzimidazole (5.84 g, 12.0 mmol) in acetic acid (glacial, 100 mL) add ammonium acetate (9.26 g, 120 mmol) and copper (I) acetate (4.31 g, 23.7 mmol), followed by 2,6-difluorobenzaldehyde (1.41 mL, 13.1 mmol), and stir the mixture at 100° C. for 4 hours. Cool the mixture to 0° C. and slowly pour over a mixture of NH4Cl/NH4OH 3:1, pH=9. Dilute the mixture with H2O (200 mL), extract with EtOAc (3×200 mL), wash with saturated aqueous NaCl (150 mL), dry (Na2SO4), and concentrate in vacuo. Purify the residue in a biotage system (eluent:CH2Cl2/MeCN 5:1), and then by HPLC, to afford a yellow solid, 675 mg, 11% yield. MS(ES+): m/z=495.0 (M+H)+

Provenance & Evidence