4-(BENZYLOXY)-3-BROMOPYRIDINE synthesis

Yield:1019767-63-5 98.6%

Reaction Conditions:

Stage #1: 3-bromo-4-hydroxypyridinewith sodium hydride in N,N-dimethyl-formamide;mineral oil at 0; for 0.333333 h;Inert atmosphere;
Stage #2: benzyl bromide in N,N-dimethyl-formamide;mineral oil at 25; for 16 h;Inert atmosphere;

Steps:

43.1 Step 1: 4-(benzyloxy)-3-bromopyridine

To a solution of 3-bromopyridin-4-ol (0.13 mL, 1.16 mmol) in DMF (2 mL) was added NaH (92 mg, 2.30 mmol, 60% dispersion in mineral oil) in portions at 0 °C under N2 atmosphere and the reaction was stirred at 0 °C for 20 min. BnBr (0.21 mL, 1.76 mmol) was added to the above mixture and the resulting mixture was stirred at 25 °C for 16 hrs. The reaction was quenched with water (20 mL) at 0 °C and the mixture was extracted with EtOAc (3 x 15 mL). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by column chromatography (PE: EtOAc= 50: 1 to 20: 1) to give the title compound (300 mg, 98.6% yield) as light yellow solid. LC/MS (ESI) m/z: 264 (M+H)⁺.

References:

WO2022/34568,2022,A1 Location in patent:Paragraph 0268