Phosphorus oxychloride → 4-Chloro-5-fluoro-2-(4-fluorobenzyl)-pyrimidine

A mixture of 1.93 g (8.7 mmol) of 5-fluoro-2-(4-fluorobenzyl)-4-hydroxypyrimidine, from Step 1, and 15 mL of phosphorus oxychloride was heated in an oil bath at 90° C. for 1.5 hours and then concentrated in vacuo. The residue was triturated with 75 mL of ice water and the aqueous mixture was adjusted to pH 8-9 by the addition of solid sodium bicarbonate. The mixture was extracted with 3×70 mL of methylene chloride. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to a light brown residue. The residue was purified by flash chromatography on a 230-400 mesh silica gel column (4.8×14.6 cm) eluted with hexane:methylene chloride (1:1 v/v) to afford 1.94 g (90% yield) of the title compound; MS DCI-NH3M/Z: 241 (M+H)+ ; 1H NMR (CDCl3) d 4.22 (s, 2H), 7.00 (m, 2H), 7.30 (m, 2H), 8.48 (s, 1H).

1. concentrationconcentrated in vacuo
2. customThe residue was triturated with 75 mL of ice water
3. additionthe aqueous mixture was adjusted to pH 8-9 by the addition of solid sodium bicarbonate
4. extractionThe mixture was extracted with 3×70 mL of methylene chloride
5. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo to a light brown residue
8. customThe residue was purified by flash chromatography on a 230-400 mesh silica gel column (4.8×14.6 cm)
9. washeluted with hexane:methylene chloride (1:1 v/v)

ORDレコード

ord-18e20e45dab2487986293b0e9a59cfbd

出典データセット

uspto-grants-1997_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05599816