Reaction #48786

Reaction equation

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

Yield 22.3%

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

Yield 22.3%

Solvents

DCM

Conditions

Workup

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

Procedure

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).

Source