تفاعل #72818

معادلة التفاعل

NaOH

2-methyl-6-(4-morpholinyl)-1-(phenylmethyl)-1H-benzimidazol-4-amine

NaNO2

NaBr

→

desired product

المردود 58.0%

4-bromo-2-methyl-6-(4-morpholinyl)-1H-benzimidazole

المردود 58.0%

المذيبات

HBr

water

HBr

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONAfter addition the mixture
2. 2
   درجة الحرارةThe resulting mixture was then heated to 80° C. for 30 minutes
3. 3
   درجة الحرارةcooled to room temperature
4. 4
   استخلاصextracted with EtOAc (100 mL×3)
5. 5
   تركيزThe combined organic layers were concentrated in-vacuum
6. 6
   أخرىthe residue was purified by silica gel chromatography
7. 7
   غسيلeluted with petroleum ether

الإجراء التجريبي

To a solution of 2-methyl-6-(4-morpholinyl)-1-(phenylmethyl)-1H-benzimidazol-4-amine (2.3 g, 10 mmol) in aqueous HBr (50 mL) was added a solution of NaNO2 (720 mg, 10.5 mmol) in water (10 mL) dropwise at 0-5° C. After addition the mixture was stirred at 0° C. for 5 minutes, another solution of NaBr (3.1 g, 30 mmol) in aqueous HBr (50 mL) was added dropwise at 60° C. The resulting mixture was then heated to 80° C. for 30 minutes and then cooled to room temperature. It was neutralized with aqueous 2N NaOH and extracted with EtOAc (100 mL×3). The combined organic layers were concentrated in-vacuum and the residue was purified by silica gel chromatography eluted with petroleum ether:EtOAc=1:1 to give the desired product (1.7 g, 58%) as a white solid. 1H NMR (300 MHz, DMSO-d6): δ ppm 2.44 (s, 3H), 3.07 (t, 4H, J=4.8 Hz), 3.74 (t, 4H, J=4.8 Hz), 6.85 (d, 1H, J=1.8 Hz), 7.04 (d, 1H, J=1.8 Hz), 12.20 (br s, 1H); LC-MS: m/e=296 [M+1]+

المصدر