Pyridine → HCID 178457486, compound

Participants

Reaction Steps

To a stirred solution of 5-benzyloxy-2-(2-bromo-4-chlorobenzyl)-6-hydroxypyrimidine-4-carboxylic acid (377) (4.0 g, 8.9 mmol) in tetrahydrofuran (150 mL) was added [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropyl-amine (8b) (5.8 g, 26.73 mmol). To the reaction mixture, pyridine (2.159 mL, 26.726 mmol) was added, followed very slow addition of POCl3 (2.454 mL, 26.726 mmol) at −15° C. the resulting reaction mixture was stirred for 2 h at same temperature. 2 drops of dimethylformamide were added to the reaction mixture which was thereafter allowed to stir at room temperature for 16 h while silica thin layer chromatography was performed (50% ethyl acetate in hexane; Rf=0.5). After completion of the reaction, the reaction mixture was quenched with ice cold water (150 mL) and extracted with ethyl acetate (2×250 mL). The combined organic parts were dried and concentrated and the resulting crude residue was purified on a column (normal silica 100-200 mesh) to get 5-benzyloxy-2-(2-bromo-4-chlorobenzyl)-6-hydroxypyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (378) (2.9 g, 50.15%) as a colorless gummy liquid.

Provenance & Evidence