Ammonia → 1-Methyl-3-phenylpiperazine

A reactor was charged with 515 kg of toluene, 1320 kg of dimethylformamide, 41 kg of tetrabutylammonium bromide and 1392 kg of a 28% aqueous ammonia. A slurry mixture of 524.3 kg (pure content: 409.9 kg) of the wet crystals of N-(2-chloroethyl)-N-methyl-α-chloro-β-phenylethylamine hydrochloride obtained in Example 9 and 519.2 kg of toluene was introduced thereinto. A vessel in which the slurry mixture had been placed was washed with 178 kg of toluene, and the washing liquid was introduced into the reactor. The mixture was stirred at 40° to 44° C. for 2 hours, and the termination point of the reaction was confirmed by gas chromatography. A solution prepared by dissolving 109 kg of sodium hydroxide in 246.3 kg of a 25% aqueous sodium hydroxide was added thereto to adjust its pH to 11.7. The mixture was stirred at 45° to 47° C. for 2 hours, and allowed to separate into layers. To the aqueous layer was added a solution prepared by dissolving 31 kg of sodium hydroxide in 71 kg of a 25% aqueous sodium hydroxide, and the resulting mixture was stirred and extracted at 23° to 24° C. with 461 kg of toluene. Further, 461 kg of toluene was added to the aqueous layer with stirring to extract. The organic layers were combined, and the combined organic layer was dried over 76 kg of anhydrous magnesium sulfate. The organic layer was filtered, and the filtered residue was washed with 143 kg of toluene. The filtrate was concentrated under reduced pressure to distill off toluene. Further, dimethylformamide was distilled off under reduced pressure (450 to 720 Pa), and thereafter, 157.8 g of 1-methyl-3-phenylpiperazine was obtained as a main component (yield: 58.7%). Its boiling point was from 98° to 122° C. (0.2 to 2 kPa).

1. additionwas introduced
2. washA vessel in which the slurry mixture had been placed was washed with 178 kg of toluene
3. additionthe washing liquid was introduced into the reactor
4. customA solution prepared
5. additionwas added
6. stirringThe mixture was stirred at 45° to 47° C. for 2 hours
7. customto separate into layers
8. additionTo the aqueous layer was added a solution
9. customprepared
10. stirringthe resulting mixture was stirred
11. extractionextracted at 23° to 24° C. with 461 kg of toluene
12. additionFurther, 461 kg of toluene was added to the aqueous layer
13. stirringwith stirring
14. extractionto extract
15. dry with materialthe combined organic layer was dried over 76 kg of anhydrous magnesium sulfate
16. filtrationThe organic layer was filtered
17. washthe filtered residue was washed with 143 kg of toluene
18. concentrationThe filtrate was concentrated under reduced pressure
19. distillationto distill off toluene
20. distillationFurther, dimethylformamide was distilled off under reduced pressure (450 to 720 Pa)

ORD record

ord-dba617f027fc4d07842c3830b679e323

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06495685B1