반응 #48807

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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

수율 30.9%

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

수율 30.9%

용매

DCM

반응 조건

후처리

1. 1
   여과The reaction mixture was filtered through celite
2. 2
   세척washed with DCM (2×10 mL)
3. 3
   기타the DCM removed in vacuo
4. 4
   기타The residue was partitioned between ethyl acetate
5. 5
   세척a saturated solution of sodium bicarbonate, the organic layer washed with brine
6. 6
   건조dried (MgSO4)
7. 7
   농축concentrated 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
    추출extracted with ethyl acetate (20 mL)
12. 12
    세척The organic layer was washed with brine
13. 13
    건조dried (MgSO4)
14. 14
    농축concentrated in vacuo
15. 15
    기타The residue was chromatographed on silica
16. 16
    세척eluting with ethyl acetate

실험 절차

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).

출처