反応 #339804

反応方程式

4-bromo-2,2-diphenylbutyronitrile

2-methylimidazole

dimethylsulfoxide

phosphoric acid

→

4-(2-methylimidazole-1-yl)-2,2-diphenylbutyronitrile phosphate

収率 74.5%

溶媒

ethanol

ethanol

water

ethyl acetate

反応条件

後処理

1. 1
   workup.STIRRINGat an inner temperature of 39° C., and the mixture was stirred for 5 minutes
2. 2
   その他organic layer was separated
3. 3
   洗浄After washing the organic layer with 2 L of water
4. 4
   濃縮2 L of 2.5% acetic acid, the organic layer was concentrated under reduced pressure
5. 5
   workup.ADDITIONwas added dropwise at an inner temperature of 31° C.
6. 6
   workup.STIRRINGunder stirring
7. 7
   workup.ADDITIONthis dropwise addition
8. 8
   workup.ADDITIONwere added dropwise)
9. 9
   その他the precipitation of crystals
10. 10
    workup.STIRRINGby stirring for 30 minutes
11. 11
    workup.ADDITIONwas added dropwise
12. 12
    workup.STIRRINGsuccessively the solution was stirred for 16 hours at an inner temperature of 30° C
13. 13
    ろ過The precipitated crystals were collected by filtration
14. 14
    洗浄after washing them with 1 L of ethanol
15. 15
    その他the crystals were dried for 5 hours at 60° C. under reduced pressure (vacuum pump)

実験手順

A mixture of 500 g (1.67 mol) of 4-bromo-2,2-diphenylbutyronitrile, 685 g (8.34 mol) of 2-methylimidazole and 250 mL of dimethylsulfoxide (DMSO) was stirred for 5 hours at 95 to 105° C., and then cooled with ice water. After 2 L of ethyl acetate and 2 L of water were added therein at an inner temperature of 39° C., and the mixture was stirred for 5 minutes, organic layer was separated. After washing the organic layer with 2 L of water and then 2 L of 2.5% acetic acid, the organic layer was concentrated under reduced pressure. The residual oil was dissolved in 2 L of ethanol and to this solution a solution of 192 g (1.67 mol) of 85% phosphoric acid and 1 L of ethanol was added dropwise at an inner temperature of 31° C. under stirring, and this dropwise addition was interrupted when the solution became milky white (about 500 mL were added dropwise). After confirming the precipitation of crystals by stirring for 30 minutes, remaining phosphoric acid solution was added dropwise, and successively the solution was stirred for 16 hours at an inner temperature of 30° C. The precipitated crystals were collected by filtration and, after washing them with 1 L of ethanol, the crystals were dried for 5 hours at 60° C. under reduced pressure (vacuum pump) to obtain 496 g (74.5%) of 4-(2-methylimidazole-1-yl)-2,2-diphenylbutyronitrile phosphate. Out of these crystals, 100 g were completely dissolved with stirring into a mixture of 100 mL of purified water and 400 mL of 2-propanol and to this solution 500 mL of 2-propanol were added under stirring, followed by cooling with ice water. After stirring this solution for 1 hour at an inner temperature of below 15° C., the precipitated crystals were collected by filtration which were then washed with 100 mL of 2-propanol, then with 100 mL of ethyl acetate. The crystals were dried for 17 hours at 60° C. under reduced pressure (vacuum pump) to obtain 91.3 g (Total yield: 68%) of purified product of 4-(2-methylimidazole-1-yl)-2,2-diphenylbutyronitrile phosphate as white crystalline powder with hygroscopicity. After a mixture of 80.0 g (200 mmol) of the purified product thus obtained, 132 g (2.02 mol) of 86% potassium hydroxide and 400 ml of 2-propanol was refluxed for 5 hours under an atmosphere of argon, the mixture was cooled with ice water. Under stirring, 800 mL of 2 mol/L hydrochloric acid were added into the mixture at an inner temperature of 30° C. (temperature was raised to 50° C.) to crystallize out of the mixture, and, after stirring for 1 hour at an inner temperature of below 15° C., the crystals were collected from the solution by filtration. These crystals were washed with a mixture of 30 mL of 2-propanol and 60 mL of purified water, then with each 250 mL of purified water five times (fifth washed solution: pH 8.80). The crystals were dried for 16 hours at 40° C. in blower to obtain 55.2 g (86.4%) of crude crystals. Into a mixed solution of 200 mL of 95% 2-propanol, 27.6 g out of these were dissolved completely by heating, which was then stirred for 1 hour at room temperature to crystallize out of the solution, followed by cooling with ice water. After stirring the solution for 1 hour at an inner temperature of below 15° C., the precipitated crystals were collected by filtration and washed with 10 mL of 2-propanol. The crystals were dried for 3 hours at 60° C. under reduced pressure (vacuum pump) to obtain 25.7 g (Total yield: 80%) of crude crystals of 4-(2-methylimidazole-1-yl)-2,2-diphenylbutanamide as white crystalline powder.

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