Reacción #48807

Ecuación de reacción

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

Rendimiento 30.9%

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

Rendimiento 30.9%

Disolventes

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   FiltraciónThe reaction mixture was filtered through celite
2. 2
   Lavadowashed with DCM (2×10 mL)
3. 3
   Otrothe DCM removed in vacuo
4. 4
   OtroThe residue was partitioned between ethyl acetate
5. 5
   Lavadoa saturated solution of sodium bicarbonate, the organic layer washed with brine
6. 6
   Secadodried (MgSO4)
7. 7
   Concentraciónconcentrated 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
    Extracciónextracted with ethyl acetate (20 mL)
12. 12
    LavadoThe organic layer was washed with brine
13. 13
    Secadodried (MgSO4)
14. 14
    Concentraciónconcentrated in vacuo
15. 15
    OtroThe residue was chromatographed on silica
16. 16
    Lavadoeluting with ethyl acetate

Procedimiento

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).

Fuente