反応 #48786

反応方程式

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

収率 22.3%

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

収率 22.3%

溶媒

DCM

反応条件

後処理

1. 1
   ろ過The reaction mixture was filtered
2. 2
   洗浄washed with DCM (2×10 mL)
3. 3
   その他evaporated in vacuo
4. 4
   その他the residual oil partitioned between ethyl acetate (25 mL) and 1M hydrochloric acid (10 mL)
5. 5
   その他The ethyl acetate layer was separated
6. 6
   洗浄washed sequentially with aqueous sodium hydrogen carbonate solution and brine
7. 7
   乾燥dried (MgSO4)
8. 8
   その他evaporated to a residue which
9. 9
   その他was chromatographed by preparative HPLC on C18 reversed phase

実験手順

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).

出典