Tert-butyl 3-formylazetidine-1-carboxylate → tert-Butyl-3-((4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(hydroxy)methyl)azetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (1.0 g, 2.32 mmol, Intermediate 47: step d) was added THF (30 mL) resulting in a colorless homogeneous mixture. The solution was cooled to −70° C. and then n-BuLi (2.5M in hexanes, 1.08 mL, 2.69 mmol)) was added drop wise. The color of the solution became a dark opaque reddish-brown color. After 2 min, tert-butyl 3-formylazetidine-1-carboxylate (545 mg, 2.94 mmol, in 3 mL THF) was introduced. After 5 min, the reaction mixture was placed in an ice-water bath and allowed to stir for 30 min at which time the mixture was quenched with NH4Cl solution. The contents were diluted further with water and extracted with EtOAc (5×40 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to provide a yellow foam. The crude material was chromatographed on silica gel (20% EtOAc-Hexanes increasing to 50% EtoAc) to give the title compound (950 mg) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.06 (d, J=1.7 Hz, 1H), 7.84 (d, J=8.6 Hz, 1H), 7.63 (dd, J=8.6, 1.9 Hz, 1H), 7.50 (d, J=8.2 Hz, 2H), 7.38 (d, J=8.1 Hz, 2H), 4.99 (dd, J=8.0, 3.3 Hz, 1H), 4.35 (s, 2H), 4.05 (bs, 2H), 3.82 (t, J=8.7 Hz, 1H), 3.74-3.67 (m, 1H), 2.99-2.90 (m, 1H), 2.20-2.15 (m, 1H), 1.41 (s, 9H). MS (ESI): mass calcd. for C27H28ClF3N2O4: 536.98, m/z found 537.2 [M+H]+.

Provenance & Evidence