Reaction #48846

Reaction equation

3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

4-ethoxycarbonylphenylboronic acid

triethylamine

→

desired compound

Yield 62.1%

Ethyl 4-(3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenoxy)benzoate

Yield 62.1%

Solvents

DCM

Conditions

Workup

1. 1
   FiltrationThe reaction mixture was filtered through celite
2. 2
   Washwashed with DCM (2×50 mL)
3. 3
   OtherThe DCM was removed in vacuo
4. 4
   Otherthe residual oil partitioned between ethyl acetate (100 mL) and water (100 mL)
5. 5
   Filtrationfiltered
6. 6
   Washthe ethyl acetate layer washed with brine (50 mL)
7. 7
   Dryingdried (MgSO4)
8. 8
   Otherevaporated to a residue which
9. 9
   Otherwas chromatographed on silica
10. 10
    Washeluting with a gradient of 50-100% ethyl acetate in isohexane

Procedure

A suspension of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (4.5 g, 0.011 mol), 4-ethoxycarbonylphenylboronic acid (3.24 g, 0.016-mol), copper (II) acetate (3.06 g, 0.016 mol), triethylamine (7.74 mL, 0.055 mol) and freshly activated 4 Å molecular sieves (13 g) in DCM (180 mL) was stirred at ambient temperature and under ambient atmosphere for 3 days. The reaction mixture was filtered through celite, washed with DCM (2×50 mL). The DCM was removed in vacuo and the residual oil partitioned between ethyl acetate (100 mL) and water (100 mL), filtered and the ethyl acetate layer washed with brine (50 mL), dried (MgSO4), and evaporated to a residue which was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (3.78 g).

Source