反応 #72800

反応方程式

methyl 2,3-diamino-5-(4-morpholinyl)benzoate

CF3COOH

→

desired product

methyl 5-(4-morpholinyl)-2-(trifluoromethyl)-1H-benzimidazole-7-carboxylate

反応条件

後処理

1. 1
   温度was heated
2. 2
   温度at reflux temperature for 8 h
3. 3
   その他consumption of starting material
4. 4
   その他the solvent was removed in-vacuo
5. 5
   workup.ADDITIONThe residue was diluted with aqueous NaHCO3
6. 6
   抽出extracted with EtOAc (250 mL×3)
7. 7
   洗浄The combined organic layers were washed with brine (250 mL×2)
8. 8
   乾燥dried over anhydrous Na2SO4
9. 9
   ろ過After filtration
10. 10
    その他the solvent was removed by rotary evaporator
11. 11
    その他The residue was then purified by silica gel chromatography
12. 12
    洗浄eluted with EtOAc

実験手順

A mixture of methyl 2,3-diamino-5-(4-morpholinyl)benzoate (4.0 g) in CF3COOH (20 mL) was heated at reflux temperature for 8 h. When TLC analysis indicated consumption of starting material, the mixture was cooled to room temperature and the solvent was removed in-vacuo. The residue was diluted with aqueous NaHCO3 and extracted with EtOAc (250 mL×3). The combined organic layers were washed with brine (250 mL×2), dried over anhydrous Na2SO4. After filtration, the solvent was removed by rotary evaporator. The residue was then purified by silica gel chromatography eluted with EtOAc:petroleum ether=1:4 to afford the desired product as a pale solid. (4.3 g, 82.7%). 1H NMR (300 MHz, DMSO-d6): δ ppm 13.47 (s, 1H), 7.71 (s, 1H), 7.56 (s, 1H), 3.96 (s, 3H), 3.79 (t, 4H, J=4.5 Hz), 3.17 (s, 4H). LC-MS: m/e=330.1 [M+1]+.

出典