Reaktion #48786

Reaktionsgleichung

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

Ausbeute 22.3%

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

Ausbeute 22.3%

Lösungsmittel

DCM

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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).

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