Pyridine → 3-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1-(3-trifluoromethoxy-phenyl)-1,3-dihydro-indol-2-one

Participants

Reaction Conditions

Reaction Steps

Using a method similar to Preparation 38, with 3-[4-(tert-Butyl-dimethylsilanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1,3-dihydro-indol-2-one (15.34 g, 40 mmol), 3-(trifluoromethoxy)phenylboronic acid (16.47 g, 80 mmol), copper (II) acetate (7.27 g, 40 mmol), pyridine (6.5 ml, 80 mmol) and powdered 4A sieves (25 g) in dichloromethane (130 mL) and heat at 32° C. for 1 day stirring mechanically. Add more 3-(trifluoromethoxy)phenylboronic acid (8.24 g, 40 mmol), copper (II) acetate (3.64 g, 20 mmol), pyridine (6.5 ml, 80 mmol) and powdered 4A sieves (25 g) and continue heating for 1 day. Dilute with ethyl acetate (150 mL) and filter slowly through a pads of Celite and silica gel. After the filtration is complete stir the pads in additional ethyl acetate and refilter. Evaporate the organics in vacuo and apply the resulting residue to a silica pad with dichloromethane/acetone. Elute with 2% ethyl acetate/dichloromethane and concentrate in vacuo to obtain 17.45 g of a yellow solid. Titurate the solid in diethyl ether, filter, and dry to obtain 9.47 g (44%) of a white solid. MS (ES): m/z=526 (M+1−H2O); 1H NMR (DMSO-d6): δ7.71 (t, 1H), 7.58-7.52 (m, 3H), 7.32-7.25 (m, 2H), 7.13 (t, 1H), 7.01 (s, 2H), 6.87 (d, 1H), 6.76 (s, 1H), 2.14 (s, 6H), 0.99 (s, 9H), 0.17 (s, 6H).

Provenance & Evidence