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

HRID 1844

Reaktionsgleichung

Reaktionsgleichung von HRID 1844
[F:1][C:2]1[C:3](O)=[N:4][C:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.P(Cl)(Cl)([Cl:19])=O>>[Cl:19][C:3]1[C:2]([F:1])=[CH:7][N:6]=[C:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[N:4]=1

Komponenten

3

Edukt 2

HCID 24813Phosphorus oxychlorideHCID 1784182335-Fluoro-2-(4-fluorobenzyl)-4-hydroxypyrimidine

Produkt 1

HCID 196913544-Chloro-5-fluoro-2-(4-fluorobenzyl)-pyrimidineAusbeute 90 %

Versuchsvorschrift

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).

Aufarbeitung

  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 X 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 X 14.6 cm)
  9. washeluted with hexane:methylene chloride (1:1 v/v)

Quellen und Nachweise

ORD-Eintrag
ord-9f25fd50f39249598d47f6ff669d7346
Quelldatensatz
uspto-grants-1998_03
Patentnummer
US05726182

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