反応 #45329

反応方程式

potassium bis(trimethylsilyl)amide

H2O

1-[5′-Isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine

3,5-Bis(trifluoromethyl)benzyl bromide

→

[3,5-bis(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amine

溶媒

THF

toluene

反応条件

後処理

1. 1
   抽出The mixture was extracted with EtOAc (75 mL)
2. 2
   洗浄The organic layer was washed with brine (25 mL)
3. 3
   乾燥dried over Na2SO4
4. 4
   ろ過filtered
5. 5
   濃縮concentrated
6. 6
   その他Purification by flash chromatography with 0 to 15% EtOAc/hexanes

実験手順

1-[5′-Isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine (94.1 mg, 0.291 mmol) was dissolved in THF (4 mL). 3,5-Bis(trifluoromethyl)benzyl bromide (320 μL, 1.75 mmol) was added followed by potassium bis(trimethylsilyl)amide (2.33 mL of a 0.5 M solution in toluene, 1.164 mmol). The reaction was stirred at room temperature for 72 hours and then poured into H2O (30 mL). The mixture was extracted with EtOAc (75 mL). The organic layer was washed with brine (25 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 0 to 15% EtOAc/hexanes, then a second column with 50% CH2Cl2, then a third column with 25% EtOAc/hexanes afforded [3,5-bis(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amine as a light yellow oil. Rf=0.18 (40% CH2Cl2/hexanes). LCMS=550.3 (M+1)+. 1H NMR (CDCl3, 600 MHz) δ 7.75 (s, 1H), 7.74 (s, 1H), 7.70 (s, 2H), 7.58 (d, J=7.9 Hz, 1H), 7.34 (d, J=7.8 Hz, 1H), 7.24 (dd, J=8.5, 2.2 Hz, 1H), 6.99 (d, J=2.2 Hz, 1H), 6.90 (d, J=8.5 Hz, 1H), 3.68-3.76 (m, 4H), 3.68 (s, 3H), 2.88 (m, 1H), 1.22 (d, J=6.4 Hz, 6H).

出典