2,6-Lutidine → tert-Butyl-3-((4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)(hydroxy)methyl)azetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A flask containing 2,6-dimethylpyridine (277 mg, 1.49 mmol) and THF (5 mL) was cooled to −78° C. and then n-BuLi (2.5 M in hexanes, 0.610 mL, 1.52 mmol) was added dropwise producing a homogeneous orange solution. After 3 minutes, tert-butyl 3-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline-6-carbonyl)azetidine-1-carboxylate (505 mg, 0.94 mmol, Intermediate 61: step b) in 3 mL THF was introduced. After 5 minutes, the −78° C. bath was replaced with an ice-water bath. After 30 minutes, the reaction mixture was quenched with aqueous NH4Cl solution and extracted with EtOAc (3×30 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. This material was combined with a batch from a duplicate experiment for chromatography on silica gel (5% acetone-DCM increasing to 30% acetone with 1% MeOH) which provided the title compound as an off white amorphous solid. 1H NMR (500 MHz, CDCl3) δ 8.10 (d, J=1.8 Hz, 1H), 7.73 (dd, J=8.7, 1.5 Hz, 1H), 7.60 (d, J=8.1 Hz, 1H), 7.51 (d, J=7.9 Hz, 2H), 7.37 (dd, J=25.7, 8.4 Hz, 4H), 7.05 (d, J=8.0 Hz, 1H), 4.34 (s, 2H), 4.12-4.02 (m, 5H), 3.93-3.84 (m, 1H), 3.78-3.71 (m, 1H), 3.59-3.49 (m, 1H), 2.70 (s, 1H), 2.51 (s, 3H), 2.14 (s, 3H), 1.41 (s, 9H); MS (ESI): mass calcd. Chemical Formula: C34H35ClF3N3O4, Exact Mass: 641.2. m/z found 641.9 [M+H]+.

Provenance & Evidence