Reaktion #626412

Reaktionsgleichung

1-(bromomethyl)-2-methyl-3-(trifluoromethyl)benzene

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

K2CO3

→

desired product

Ausbeute 98.0%

methyl 2-(difluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazole-4-carboxylate

Ausbeute 98.0%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeprepared
2. 2
   TemperaturThe reaction mixture was cooled to room temperature
3. 3
   Filtrationfiltered
4. 4
   workup.ADDITIONThe filtrate was poured into water (100 mL)
5. 5
   Filtrationfiltered
6. 6
   Sonstigethe filter cake was collected
7. 7
   Sonstigepurified by silica gel chromatography
8. 8
   Wascheneluted with petroleum ether

Vorschrift

A mixture of methyl 2-(difluoromethyl)-5-(4-morpholinyl)-1H-benzimidazole-7-carboxylate, prepared as described in Example 68 (500 mg, 1.6 mmol), K2CO3 (442 mg, 3.2 mmol) and 1-(bromomethyl)-2-methyl-3-(trifluoromethyl)benzene (480 mg, 1.9 mmol) in DMF (15 mL) was stirred at 70° C. for 18 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was poured into water (100 mL) and filtered, the filter cake was collected and purified by silica gel chromatography eluted with petroleum ether:EtOAc=1:1 to give the desired product (710 mg, 98%) as a yellow solid. 1H NMR (300 MHz, DMSO-d6): δ ppm 2.53 (s, 3H), 3.14 (t, 4H, J=4.5 Hz), 3.73 (t, 4H, J=4.5 Hz), 3.93 (s, 3H), 5.75 (s, 2H), 6.27 (d, 1H, J=7.8 Hz), 7.22 (t, 1H, J=7.8 Hz), 7.30 (d, 1H, J=2.1 Hz), 7.36 (t, 1H, J=51.6 Hz), 7.58-7.61 (m, 2H); LC-MS: m/e=484 [M+1]+

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