Hydrochloric Acid → HCID 53237072, compound

Participants

Reaction Conditions

Reaction Steps

A 25 mL round bottom flask was charged with 2-chloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile (250 mg, 0.949 mmol), 1-(3-bromo-5-fluoro-pyridin-4-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethanol (332 mg, 0.949 mmol), 2M aqueous sodium carbonate (0.95 mL, 1.90 mmol) and DMF (5 mL). The reaction mixture was evacuated and flushed with N2 twice followed by addition of PdCl2(dppf).CH2Cl2 adduct (38.7 mg, 0.047 mmol). The reaction was stirred under N2 at 100° C. for 3 days. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and washed with water twice. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude was dissolved in DMF (5 mL) and 4M HCl solution in dioxane (2.372 mL, 9.49 mmol). The reaction mixture was stirred at room temperature for 1 hr. The reaction mixture was quenched with saturated NaHCO3 solution and extracted with DCM twice. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude was purified by silica gel flash chromatography employing DCM-MeOH (9:1) to afford 2-chloro-4-[4-(1,2-dihydroxy-ethyl)-5-fluoro-pyridin-3-yl]-benzonitrile. 1H NMR (400 MHz, MeOD) δ ppm 3.72-4.03 (m, 1H), 4.80 (t, J=6.8 Hz, 1H), 7.61 (dd, J=8.0, 1.6 Hz, 1H), 7.82 (d, J=1.3 Hz, 1H), 7.95 (d, J=8.1 Hz, 1H), 8.31 (s, 1H), 8.55 (d, J=2.5 Hz, 1H); HRMS: (ESI) ink 293.0488 [(M+H)+ Calcd for C14H10ClFN2O2 293.0493].

Provenance & Evidence