تفاعل #304239

معادلة التفاعل

HMPA

6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde

methyl sulfone

n-BuLi

→

crude desired product

المردود 97.1%

1-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-2-methanesulfonyl-ethanol

المردود 97.1%

المذيبات

THF

THF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGAfter stirring for additional 10 minutes
2. 2
   workup.STIRRINGThe resulting solution is stirred for 1.5 hours at −78° C
3. 3
   أخرىThe reaction is quenched with saturated aqueous NH4Cl
4. 4
   workup.ADDITIONdiluted with EtOAc
5. 5
   غسيلThe organic layer is washed with water
6. 6
   تجفيفdried over MgSO4
7. 7
   ترشيحfiltered
8. 8
   تركيزconcentrated in vacuo
9. 9
   أخرىpurified by flash chromatography (3% MeOH in CH2Cl2)

الإجراء التجريبي

To a solution of methyl sulfone (65 mg, 0.68 mmol) in THF (1.5 mL) is added a solution of n-BuLi (0.27 mL, 0.68 mmol, 2.5 M solution in hexane) at −78° C. After stirring for 5 minutes, HMPA (0.1 mL) is added. After stirring for additional 10 minutes, a solution of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde 10f (26 mg, 0.069 mmol) in THF (1 mL) is added. The resulting solution is stirred for 1.5 hours at −78° C. The reaction is quenched with saturated aqueous NH4Cl, warmed to room temperature, and diluted with EtOAc. The organic layer is washed with water, dried over MgSO4, filtered, concentrated in vacuo, and purified by flash chromatography (3% MeOH in CH2Cl2) to give the crude desired product (31 mg, 96%) which is used directly without further purification: MS APCI (+) m/z 462, 464 (M+, Br pattern) detected.

المصدر