Реакция #48807

Уравнение реакции

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

3-fluoro-4-methoxyphenylboronic acid

triethylamine

→

desired compound

Выход 30.9%

3-(3-Fluoro-4-methoxyphenoxy)-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Выход 30.9%

Растворители

DCM

Условия реакции

Обработка

1. 1
   ФильтрацияThe reaction mixture was filtered through celite
2. 2
   Промывкаwashed with DCM (2×10 mL)
3. 3
   Другоеthe DCM removed in vacuo
4. 4
   ДругоеThe residue was partitioned between ethyl acetate
5. 5
   Промывкаa saturated solution of sodium bicarbonate, the organic layer washed with brine
6. 6
   Сушкаdried (MgSO4)
7. 7
   Концентрированиеconcentrated in vacuo
8. 8
   workup.ADDITION3.5M Hydrochloric acid (0.5 mL) was added to a solution of the residual oil
9. 9
   workup.DISSOLUTIONdissolved in methanol (5 mL)
10. 10
    workup.ADDITIONThe reaction mixture was diluted with water (10 mL)
11. 11
    Экстракцияextracted with ethyl acetate (20 mL)
12. 12
    ПромывкаThe organic layer was washed with brine
13. 13
    Сушкаdried (MgSO4)
14. 14
    Концентрированиеconcentrated in vacuo
15. 15
    ДругоеThe residue was chromatographed on silica
16. 16
    Промывкаeluting with ethyl acetate

Методика

A solution of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (0.30 g, 0.74 mmol), 3-fluoro-4-methoxyphenylboronic acid (255 mg, 1.5 mmol), copper (II) acetate (0.202 g, 1.11 mmol), triethylamine (0.517 mL, 3.71 mmol) and freshly activated 4 Å molecular sieves (1 g) in DCM (40 mL) was stirred at ambient temperature and under ambient atmosphere for 2 days. The reaction mixture was filtered through celite, washed with DCM (2×10 mL), the DCM removed in vacuo. The residue was partitioned between ethyl acetate and a saturated solution of sodium bicarbonate, the organic layer washed with brine, dried (MgSO4) and concentrated in vacuo. 3.5M Hydrochloric acid (0.5 mL) was added to a solution of the residual oil dissolved in methanol (5 mL) and stirred at RT for 20 minutes, then the solution neutralised with saturated sodium bicarbonate. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (20 mL). The organic layer was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was chromatographed on silica, eluting with ethyl acetate, to give the desired compound (95 mg).

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