2-Chloro-3-fluoropyridin-4-ol synthesis

Yield: 80%

Reaction Conditions:

Stage #1:2-chloro-3-fluoropyridine with lithium diisopropyl amide in tetrahydrofuran;hexane at -78;
Stage #2: with Trimethyl borate in tetrahydrofuran;hexane for 2 h;
Stage #3: with peracetic acid in tetrahydrofuran;hexane;water;acetic acid at 0; for 1 h;

Steps:

9
A solution of 2-chloro-3-fluoropyridine (2 mmol) in anhydrous THF (10ml) was cooled to -78⁰C. To this solution was added a solution of lithium diisopropylamide (LDA; 2.2 mmol) in hexane slowly at same temperature. After 2h at -78⁰C, to the mixture was added trimethoxyborane (0.48ml) and stirred for 2h, followed by an addition of peracetic acid (0.72 ml; 32% in dilute acetic acid). The mixture was allowed to warm to O⁰C under stirring for Ih, then cooled to -2O⁰C, sodium dithionite (0.8g in 2ml water) was added dropwise. The mixture was extracted with ethyl acetate and the extract was dried and concentrated. The residue was purified by chromatography, eluting with 1:19 MeOH:DCM to give the expected product as a white solid (80%).

References:

BTG INTERNATIONAL LIMITED WO2009/103950, 2009, A1 Location in patent:Page/Page column 22-23