Reaktion #48807

Reaktionsgleichung

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

Ausbeute 30.9%

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

Ausbeute 30.9%

Lösungsmittel

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe reaction mixture was filtered through celite
2. 2
   Waschenwashed with DCM (2×10 mL)
3. 3
   Sonstigethe DCM removed in vacuo
4. 4
   SonstigeThe residue was partitioned between ethyl acetate
5. 5
   Waschena saturated solution of sodium bicarbonate, the organic layer washed with brine
6. 6
   Trocknendried (MgSO4)
7. 7
   Einengenconcentrated 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
    Extraktionextracted with ethyl acetate (20 mL)
12. 12
    WaschenThe organic layer was washed with brine
13. 13
    Trocknendried (MgSO4)
14. 14
    Einengenconcentrated in vacuo
15. 15
    SonstigeThe residue was chromatographed on silica
16. 16
    Wascheneluting with ethyl acetate

Vorschrift

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).

Quelle