Reaktion #1940

Reaktionsgleichung

5-fluoro-2-(4-fluorobenzyl)-4-hydroxypyrimidine

phosphorus oxychloride

→

title compound

Ausbeute 90.0%

4-Chloro-5-fluoro-2-(4-fluorobenzyl)-pyrimidine

Ausbeute 90.0%

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenconcentrated in vacuo
2. 2
   SonstigeThe residue was triturated with 75 mL of ice water
3. 3
   workup.ADDITIONthe aqueous mixture was adjusted to pH 8-9 by the addition of solid sodium bicarbonate
4. 4
   ExtraktionThe mixture was extracted with 3 X 70 mL of methylene chloride
5. 5
   TrocknenThe combined organic extracts were dried over anhydrous magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo to a light brown residue
8. 8
   SonstigeThe residue was purified by flash chromatography on a 230-400 mesh silica gel column (4.8 X 14.6 cm)
9. 9
   Wascheneluted with hexane:methylene chloride (1:1 v/v)

Vorschrift

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 X 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 X 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).

Quelle