Triethylamine → HCID 18982836, compound

Participants

Reaction Steps

A mixture of 7-fluoro-5-(2-chloropropionyl)-2(1H,3H)-indolone (1.0 g, 4.14 mmol), 4-hydroxy-4-phenylpiperidine (0.74 g, 4.17 mmol) and triethylamine (1.2 ml, 8.6 mmol) in anhydrous dimethylformamide was heated to between 70 and 90° C. for 3 hours. The mixture was poured into 1N aqueous LiCl and extracted with two portions of ethyl acetate. The combined organic phase was washed with 1N HCI, water and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated to 1.6 g of a reddish solid. The crude product was purified by flash chromatography on silica gel (2×4 inches {50×100 mm}, 50% ethyl acetate/hexane eluent) to yield 0.58 g of the desired product. This product was further purified by recrystallization from acetonitrile/ether to give 0.2 g of light yellow solid; m.p. 197°-199.5° C. NMR (DMSO-d6) 11.25 (s, 1H), 7.90 (d, J=11.6 Hz, 1H), 7.82 (s, 1H), 7.42 (d, J=7.2 Hz, 2H), 7.28 (t, J=7.4 Hz, 2H), 7.17 (t, J=7.2 Hz, 1H), 4.76 (s, 1H), 4.25 (q, J=6.6 Hz, 1H), 3.66 (s, 2H), 2.88-2.63 (m, 2H), 2.60-2.55 (m, 1h), 2.49-2.38 (m, 1H), 1.88 (dt, J=12.2, 4.3 Hz, 1H), 1.77-1.49 (m, 3H), 1.16 (d, J=6.6 Hz, 3H). The mother liquors were rechromatographed to afford another 0.15 g of product for a total yield of 0.35 g (22%).

Provenance & Evidence