反応 #168468

反応方程式

1,3 dibromo-5,5 dimethyl hydantoin

6-chloro-4-(1-cyclobutylethoxy)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine

2,2,6,6-tetramethylpiperidinyl magnesium chloride lithium chloride

→

2-bromo-6-chloro-4-(1-cyclobutylethoxy)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine

溶媒

THF

THF

反応条件

後処理

1. 1
   workup.STIRRINGThe reaction was stirred for 30 minutes
2. 2
   その他The reaction was quenched with saturated NH4Cl solution (50 mL) at 0° C.
3. 3
   抽出extracted with EtOAc (2×20 mL)
4. 4
   洗浄The combined organic extracts were washed with water (20 mL) and brine (20 mL)
5. 5
   乾燥dried over anhydrous Na2SO4
6. 6
   ろ過filtered
7. 7
   濃縮concentrated
8. 8
   その他The residue was purified by silica gel chromatography (eluting with 8-10% EtOAc/petroleum ether)

実験手順

To a stirred solution of 6-chloro-4-(1-cyclobutylethoxy)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine (3.5 g, 11.73 mmol) in THF (20 mL) was added 2,2,6,6-tetramethylpiperidinyl magnesium chloride lithium chloride complex (1.0 M in THF/Toluene, 29.8 mL, 29.84 mmol) at −78° C. The resulting solution was stirred 2.5 hours and then 1,3 dibromo-5,5 dimethyl hydantoin (8.5 g, 29.84 mmol) in THF (20 mL) was added dropwise at −78° C. The reaction was stirred for 30 minutes then slowly warmed to room temperature over a period of 2 hours. The reaction was quenched with saturated NH4Cl solution (50 mL) at 0° C. and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (20 mL) and brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (eluting with 8-10% EtOAc/petroleum ether) to yield 2-bromo-6-chloro-4-(1-cyclobutylethoxy)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine. MS ES/APCl calc'd. for C20H27BrClN3O [M+H]+ 440. found 440.

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