Реакция #47445

Уравнение реакции

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

Растворители

water

ethyl acetate

toluene

Условия реакции

Обработка

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

Методика

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.

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