Реакция #48786

Уравнение реакции

3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

3,5-difluorophenylboronic acid

triethylamine

→

title compound

Выход 22.3%

3-[(3,5-Difluorophenyl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Выход 22.3%

Растворители

DCM

Условия реакции

Обработка

1. 1
   ФильтрацияThe reaction mixture was filtered
2. 2
   Промывкаwashed with DCM (2×10 mL)
3. 3
   Другоеevaporated in vacuo
4. 4
   Другоеthe residual oil partitioned between ethyl acetate (25 mL) and 1M hydrochloric acid (10 mL)
5. 5
   ДругоеThe ethyl acetate layer was separated
6. 6
   Промывкаwashed sequentially with aqueous sodium hydrogen carbonate solution and brine
7. 7
   Сушкаdried (MgSO4)
8. 8
   Другоеevaporated to a residue which
9. 9
   Другоеwas chromatographed by preparative HPLC on C18 reversed phase

Методика

A solution of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (202 mg, 0.5 mmol), 3,5-difluorophenylboronic acid (156 mg, 1.0 mmol), copper (II) acetate (182 mg, 1.0 mmol), triethylamine (252 mg, 2.5 mmol) and freshly activated 4 Å molecular sieves (1.5 g) in DCM (10 mL) was stirred at ambient temperature and under ambient atmosphere for 64 hours. The reaction mixture was filtered, washed with DCM (2×10 mL), evaporated in vacuo and the residual oil partitioned between ethyl acetate (25 mL) and 1M hydrochloric acid (10 mL). The ethyl acetate layer was separated, washed sequentially with aqueous sodium hydrogen carbonate solution and brine, dried (MgSO4), and evaporated to a residue which was chromatographed by preparative HPLC on C18 reversed phase using 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA) as eluant to give the title compound (45 mg).

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