反応 #4149

反応方程式

maleic acid

1-(4-bromo-2-aminophenyl)indoline

potassium carbonate

4-methyl-1-piperazinecarbonyl chloride hydrochloride

potassium carbonate

carbonyl chloride

→

N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide maleate

収率 39.8%

溶媒

ethanol

chloroform

water

反応条件

後処理

1. 1
   温度The reaction was refluxed for 6 hours when
2. 2
   workup.ADDITIONwas added
3. 3
   温度After refluxing overnight (about 16 hours)
4. 4
   温度the reaction was cooled
5. 5
   その他The layers were separated
6. 6
   洗浄the organic phase was washed thrice with water
7. 7
   乾燥dried over Na2SO4
8. 8
   濃縮concentrated in vacuo
9. 9
   workup.DISSOLUTIONThe residue was dissolved in 200 ml of toluene
10. 10
    workup.ADDITIONcontaining 1.5 kg of silica gel
11. 11
    洗浄Elution first with toluene
12. 12
    workup.DISSOLUTIONThis was dissolved in 100 ml of ethanol
13. 13
    その他The maleate salt was collected
14. 14
    その他dried
15. 15
    その他Recrystallization from methanol (charcoal)

実験手順

To a stirred solution, under nitrogen of 43.5 g (0.15 mole) of 1-(4-bromo-2-aminophenyl)indoline of Example 3b and 82.8 g (0.60 mole) of milled potassium carbonate in 1000 ml of chloroform was added 44.7 g (0.225 mole) of 4-methyl-1-piperazinecarbonyl chloride hydrochloride in portions over 10 minutes. The reaction was refluxed for 6 hours when an additional charge of 10.4 g (0.075 mole) of potassium carbonate and 14.9 g (0.075 mole) of the carbonyl chloride reagent was added. After refluxing overnight (about 16 hours), the reaction was cooled, treated with 500 ml of water, and stirred vigorously for 15 minutes. The layers were separated and the organic phase was washed thrice with water, dried over Na2SO4, and concentrated in vacuo. The residue was dissolved in 200 ml of toluene and adsorbed on a tall chromatography column containing 1.5 kg of silica gel packed in toluene. Elution first with toluene, then with increasing percentages of dichloromethane in toluene, (25% per step), followed by dichloromethane alone, and finally with 1% methanol in dichloromethane brought forth 24 g (overall 39% yield) of fairly pure urea. This was dissolved in 100 ml of ethanol and treated with a solution of 6.96 g (0.06 mole) of maleic acid dissolved in 50 ml of ethanol. The maleate salt was collected, dried, and found to weigh 17.3 g (22% overall), m.p. 175°-177° C. dec. Recrystallization from methanol (charcoal) afforded 12.7 g (16% overall yield) of N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide maleate, m.p. 175°-177° C. dec.

出典