反応 #48807

反応方程式

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

収率 30.9%

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

収率 30.9%

溶媒

DCM

反応条件

後処理

1. 1
   ろ過The reaction mixture was filtered through celite
2. 2
   洗浄washed with DCM (2×10 mL)
3. 3
   その他the DCM removed in vacuo
4. 4
   その他The residue was partitioned between ethyl acetate
5. 5
   洗浄a saturated solution of sodium bicarbonate, the organic layer washed with brine
6. 6
   乾燥dried (MgSO4)
7. 7
   濃縮concentrated 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
    抽出extracted with ethyl acetate (20 mL)
12. 12
    洗浄The organic layer was washed with brine
13. 13
    乾燥dried (MgSO4)
14. 14
    濃縮concentrated in vacuo
15. 15
    その他The residue was chromatographed on silica
16. 16
    洗浄eluting with ethyl acetate

実験手順

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).

出典