Triphenylarsine → (5R)-(-)-3-[4-(3-pyridyl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide

Temperatur

50 °C

A mixture of (5R)-(−)-3-[3-fluoro-4-iodophenyl]-2-oxo-5-oxazolidinecarboxamide (Step 3, 422 mg, 1.21 mmol), 3-(trimethylstannyl)pyridine (Step 4, 350 mg, 1.45 mmol), tris(dibenzylideneacetone)dipalladium(0) (22 mg, 0.0242 mmol), triphenylarsine (59 mg, 0.194 mmol) and copper(I) iodide (9 mg, 0.0484 mmol) in N-methyl-2-pyrrolidinone (4.8 mL) under nitrogen was degassed, heated up to 50° C. and stirred at this temperature for 2 days, during which additional tris(dibenzylideneacetone)dipalladium(0) (22 mg, 0.0242 mmol), triphenylarsine (59 mg, 0.194 mmol) and copper(I) iodide (9 mg, 0.0484 mmol) are added. The resulting mixture was diluted with water (15 mL) and extracted with methylene chloride (3×20 mL), and the combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting oil was diluted with ethyl acetate (25 mL) and extracted with aqueous hydrochloric acid (1M, 25 mL), and the aqueous phase was neutralized with sodium hydroxide (s), saturated with sodium chloride and extracted with methylene chloride (3×25 mL) containing a small amount of methanol. This combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate/hexane to give the title compound, mp 240-242° C. (dec.); MS (ESI+) for C15H12FN3O3 m/z 302 (M+H)+; [α]25D=−25 (c 0.94, DMSO).

1. customwas degassed
2. additionare added
3. extractionextracted with methylene chloride (3×20 mL)
4. dry with materialthe combined organic phase was dried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. additionThe resulting oil was diluted with ethyl acetate (25 mL)
7. extractionextracted with aqueous hydrochloric acid (1M, 25 mL)
8. extractionextracted with methylene chloride (3×25 mL)
9. additioncontaining a small amount of methanol
10. dry with materialThis combined organic phase was dried over anhydrous sodium sulfate
11. concentrationconcentrated under reduced pressure
12. customthe residue was recrystallized from ethyl acetate/hexane

ORD-Eintrag

ord-93ae7e3afe064a70ab6a4860f8cb8db3

Quelldatensatz

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07049443B2