Trifluoroacetic acid → HCID 20823149, compound

Participants

Reaction Steps

To a LDA solution (42 mL, 1.5 M solution in THF) in 65 mL of dry THF at −78° C., a solution of 2-(quinolin-6-yloxy)-propionic acid ethyl ester (8.61 g, 0.035 mol) in 65 mL of dry THF was cannulated in. The resulting solution is allowed to stand at −78° C. for 3 min. Solid 4-benzyloxybenzaldehyde (6.71 g, 0.032 mol) was added and resulting mixture was allowed to stand at −78° C. for 5 min until all solid dissovled in the solution. Reaction was then quenched with AcOH (6.03 mL, 0.105 mol) in 60 mL of THF at −78° C. The mixture was then diluted with Et2O and washed with sat'NH4Cl, water and brine, dried over Na2SO4, filtered and concentrated. The crude material was purified by chromatography to give 3-(4-benzyloxy-phenyl)-3-hydroxy-2-methyl-2-(quinolin-6-yloxy)-propionic acid ethyl ester in 86% yield. A of solution of 2.75 g of give 3-(4-benzyloxy-phenyl)-3-hydroxy-2-methyl-2-(quinolin-6-yloxy)-propionic acid ethyl ester (6.01 mmol), trifluoroacetic acid (2.8 mL, 36.1 mmol), triethylsilane (5.8 mL, 36.1 mmol) in 80 mL of dichloroethane was heated to reflux for 50 h. The mixture was cooled to r.t. and diluted with Et2O and washed with sat′ NaHCO3, water and brine. Organic layer was dried over Mg SO4, filtered and concentrated. Residue was purified by chromatography (5% MeOH in CH2Cl2) to give 86% of title compound as light yellow oil. 1H NMR (400 MHz, CDCl3) δδ 8.78 (dd, 1H, J=4.4, 1.6 Hz), 8.00 (d, 1H, J=9.2 Hz), 7.98 (d, 1H, J=8.8 Hz), 7.45-7.32 (m, 7H), 7.19 (d, 2H, J=8.8 Hz), 7.04 (d, 1H, J=3.2 Hz), 6.93 (d, 2H, J=8.8 Hz), 5.06 (s, 2H), 4.23 (q, 2H, J=7.1 Hz), 3.38, 3.18 (ABq, 2H, J=13.8 Hz), 1.53 (s, 3H), 1.19 (t, 3H, J=7.1 Hz). MS (ES+) m/z mass calcd for C28H28NO4 (m+1) 442, found 442.

Provenance & Evidence