Reacción #48786

Ecuación de reacción

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

Rendimiento 22.3%

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

Rendimiento 22.3%

Disolventes

DCM

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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).

Fuente