Reaction #48807

Reaction equation

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

3-fluoro-4-methoxyphenylboronic acid

triethylamine

→

desired compound

Yield 30.9%

3-(3-Fluoro-4-methoxyphenoxy)-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Yield 30.9%

Solvents

DCM

Conditions

Workup

1. 1
   FiltrationThe reaction mixture was filtered through celite
2. 2
   Washwashed with DCM (2×10 mL)
3. 3
   Otherthe DCM removed in vacuo
4. 4
   OtherThe residue was partitioned between ethyl acetate
5. 5
   Washa saturated solution of sodium bicarbonate, the organic layer washed with brine
6. 6
   Dryingdried (MgSO4)
7. 7
   Concentrationconcentrated in vacuo
8. 8
   workup.ADDITION3.5M Hydrochloric acid (0.5 mL) was added to a solution of the residual oil
9. 9
   workup.DISSOLUTIONdissolved in methanol (5 mL)
10. 10
    workup.ADDITIONThe reaction mixture was diluted with water (10 mL)
11. 11
    Extractionextracted with ethyl acetate (20 mL)
12. 12
    WashThe organic layer was washed with brine
13. 13
    Dryingdried (MgSO4)
14. 14
    Concentrationconcentrated in vacuo
15. 15
    OtherThe residue was chromatographed on silica
16. 16
    Washeluting with ethyl acetate

Procedure

A solution of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (0.30 g, 0.74 mmol), 3-fluoro-4-methoxyphenylboronic acid (255 mg, 1.5 mmol), copper (II) acetate (0.202 g, 1.11 mmol), triethylamine (0.517 mL, 3.71 mmol) and freshly activated 4 Å molecular sieves (1 g) in DCM (40 mL) was stirred at ambient temperature and under ambient atmosphere for 2 days. The reaction mixture was filtered through celite, washed with DCM (2×10 mL), the DCM removed in vacuo. The residue was partitioned between ethyl acetate and a saturated solution of sodium bicarbonate, the organic layer washed with brine, dried (MgSO4) and concentrated in vacuo. 3.5M Hydrochloric acid (0.5 mL) was added to a solution of the residual oil dissolved in methanol (5 mL) and stirred at RT for 20 minutes, then the solution neutralised with saturated sodium bicarbonate. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (20 mL). The organic layer was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was chromatographed on silica, eluting with ethyl acetate, to give the desired compound (95 mg).

Source