Reaktion #47445

Reaktionsgleichung

cyclopropylboronic acid

(S)-2-[4-(3-bromo-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester

(S)-2-[4-(3-bromo-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide

tricyclohexylphosphine

tripotassium phosphate

→

(S)-2-[4-(3-cyclopropyl-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester

Lösungsmittel

water

ethyl acetate

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe resulting mixture was sparged with nitrogen
2. 2
   Sonstigetransferred to an Emry Optimizer microwave reaction vessel
3. 3
   Sonstigedilute hydrochloric acid and separated
4. 4
   WaschenThe organic phase was washed with a saturated sodium bicarbonate solution
5. 5
   Trocknena saturated sodium chloride solution and dried over sodium sulfate
6. 6
   FiltrationThe mixture was filtered
7. 7
   Sonstigeevaporated
8. 8
   Sonstigethe residue purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 80 g, 0% to 50% ethyl acetate/hexanes) which

Vorschrift

To a mixture of (S)-2-[4-(3-bromo-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester (prepared as in Example 128, 1.2 g, 2.9 mmol), palladium(II) acetate (0.035 g, 0.15 mmol), tricyclohexylphosphine (0.084 g, 0.30 mmol), and tripotassium phosphate (2.0 g, 9.0 mmol) in toluene (8 mL) was added cyclopropylboronic acid (0.325 g, 3.8 mmol) and water (0.2 mL) and the resulting mixture was sparged with nitrogen and transferred to an Emry Optimizer microwave reaction vessel and heated at 130° C., for 2.5 h. The mixture was taken up in ethyl acetate and dilute hydrochloric acid and separated. The organic phase was washed with a saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over sodium sulfate. The mixture was filtered and evaporated and the residue purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 80 g, 0% to 50% ethyl acetate/hexanes) which afforded (S)-2-[4-(3-cyclopropyl-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester (0.80 g, 74%) as a pale yellow solid.

Quelle