反応 #76631

反応方程式

acetic acid

lithium diisopropylamide

ethyl isocyanoacetate

sodium hydride

(E)-5-(3,4-dichlorostyryl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

diethyl chlorophosphate

→

ethyl (E)-6-(3,4-dichlorostyryl)-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate

収率 12.4%

溶媒

tetrahydrofuran

dimethylformamide

ethyl acetate

water

反応条件

後処理

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for a further 30 minutes at −10° C.
3. 3
   workup.ADDITIONbefore being added to a solution
4. 4
   workup.STIRRINGThe resulting mixture was stirred at −78° C. for 2 hours
5. 5
   温度then warmed to −30° C.
6. 6
   洗浄The organic phase was washed twice with water
7. 7
   乾燥dried over magnesium sulphate
8. 8
   ろ過filtered
9. 9
   その他evaporated to dryness
10. 10
    その他The residue was chromatographed on silica gel
11. 11
    洗浄for the elution
12. 12
    workup.DISSOLUTIONThe product was dissolved in 1 ml of ethyl acetate
13. 13
    workup.WAIT10 ml of diethyl ether and left
14. 14
    その他to crystallize

実験手順

100 mg (2.5 mmol) of 60% sodium hydride disperion in mineral oil were added to a solution of 728 mg (2.2 mmol) of (E)-5-(3,4-dichlorostyryl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one in 5 ml of anhydrous dimethylformamide at room temperature under a nitrogen atmosphere and stirred for 30 minutes. The mixture was cooled to −20° C., 431 mg (2.5 mmol) of diethyl chlorophosphate were added and stirring was continued for a further 30 minutes at −10° C. before being added to a solution prepared by addition of 1.65 ml (3.3 mmol) of 2M lithium diisopropylamide to a solution of 375 mg (3.32 mmol) of ethyl isocyanoacetate in 5 ml of anhydrous tetrahydrofuran at −78° C. under a nitrogen atmosphere. The resulting mixture was stirred at −78° C. for 2 hours then warmed to −30° C. and 180 mg (3 mmol) of acetic acid were added followed by water and ethyl acetate. The organic phase was washed twice with water, dried over magnesium sulphate, filtered and evaporated to dryness. The residue was chromatographed on silica gel using ethyl acetate/methanol (49:1) for the elution. The product was dissolved in 1 ml of ethyl acetate and 10 ml of diethyl ether and left to crystallize. There was obtained 116 mg of ethyl (E)-6-(3,4-dichlorostyryl)-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate as a light-brown solid. MS: m/e 425.9 [M+H]+.

出典