반응 #48786

반응 방정식

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

수율 22.3%

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

수율 22.3%

용매

DCM

반응 조건

후처리

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

실험 절차

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).

출처