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

Temperatur

130 °C

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.

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

ORD-Eintrag

ord-b771612cc67d44dfa8803230e4435e56

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07741327B2