10H-Phenothiazine, 2-(trifluoromethyl)- → HCID 12799395, compound

HRID 1678864Notes

Reaction equation

HRID 1678864 reaction equation
[CH3:1][CH:2]1[NH:6][C:5](=O)[CH2:4][CH2:3]1.[F:8][C:9]([F:25])([F:24])[C:10]1[CH:23]=[CH:22][C:21]2[S:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[NH:13][C:12]=2[CH:11]=1.P(Cl)(Cl)(Cl)=O.[OH-].[Na+]>CCOCC.C1(C)C(C)=CC=CC=1>[CH3:1][CH:2]1[N:6]([C:5]2[CH2:4][CH2:3][CH:2]([CH3:1])[N:6]=2)[C:5]([N:13]2[C:12]3[CH:11]=[C:10]([C:9]([F:8])([F:24])[F:25])[CH:23]=[CH:22][C:21]=3[S:20][C:19]3[C:14]2=[CH:15][CH:16]=[CH:17][CH:18]=3)=[CH:4][CH2:3]1

Participants

7

Reactant 4

HCID 708210H-Phenothiazine, 2-(trifluoromethyl)-HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 660555-Methyl-2-pyrrolidone

Product 1

HCID 12799395HCID 12799395, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 7237O-XyleneSolvent2×

Procedure

A solution of 5-methyl-2-pyrrolidinone (19.8 g., 0.2 mole) in 25 ml. of xylene is added drop-wise to a mixture of 2-trifluoromethylphenothiazine (26.7 g., 0.1 mole) and phosphorus oxychloride (15.3 g., 0.1 mole) in 125 ml. of refluxing xylene in a 2 hour period. When the addition is complete, refluxing is continued for an additional 1.5 hr., the reaction mixture poured into 75 ml. of 5 N sodium hydroxide and 75 g. of crushed ice, and, after mixing well, the xylene fraction is separated. The xylene fraction is sequentially extracted with 100 ml. of 1.5 HCl followed by 100 ml. of water and then made basic by stirring with 5 N sodium hydroxide solution. Separation of the basified xylene fraction which is dried over magnesium sulfate and concentrated under reduced pressure provides a residue which is taken up in 50 ml. of benzene and the solution then concentrated. An additional 100 ml. portion of benzene is added to the residue thus obtained and the solution partially concentrated until crystals begin to form. After cooling and standing, the mixture is filtered to remove recovered 2-trifluoromethylphenothiazine starting material. Concentration of the filtrate affords a residual material which is taken up in ether, extracted with 1.5 N hydrochloric acid and then with 50 ml. of water. The combined acid-aqueous extracts are made basic with sodium hydroxide and the mixture extracted with ether. The ethereal extract is dried over magnesium sulfate, filtered, and concentrated. Distillation of the residual oil through a 6 cm. column provides 10-[5-methyl-1-(5-methyl-1-pyrrolin-2-yl)-2-pyrrolin-2-yl]-2-(trifluoromethyl)phenothiazine free base, b.p. 175°-185° C./0.15 mm. Hg. The bis-pyrrolinyl phenothiazine free base is taken up in ethanol and acidified with ethanolic hydrogen chloride. Addition of ether provides the hydrochloride salt which crystallized from ethanol affords analytically pure 10-[5-METHYL-1-(5-METHYL-1-PYRROLIN-2-YL)-2-PYRROLIN-2-YL]-2-(TRIFLUOROMETHYL)PHENOTHIAZINE HYDROCHLORIDE, m.p. 250°-253° C. (dec.)(corr.).

Workup

  1. additionWhen the addition
  2. temperaturerefluxing
  3. addition, the reaction mixture poured into 75 ml
  4. additionof crushed ice, and, after mixing well
  5. customthe xylene fraction is separated
  6. extractionThe xylene fraction is sequentially extracted with 100 ml
  7. customSeparation of the basified xylene fraction which
  8. dry with materialis dried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customprovides a residue which
  11. concentrationof benzene and the solution then concentrated
  12. additionportion of benzene is added to the residue
  13. customthus obtained
  14. concentrationthe solution partially concentrated until crystals
  15. customto form
  16. temperatureAfter cooling
  17. filtrationthe mixture is filtered
  18. customto remove
  19. customrecovered 2-trifluoromethylphenothiazine starting material
  20. customConcentration of the filtrate affords a residual material which
  21. extractionextracted with 1.5 N hydrochloric acid
  22. extractionthe mixture extracted with ether
  23. extractionThe ethereal extract
  24. dry with materialis dried over magnesium sulfate
  25. filtrationfiltered
  26. concentrationconcentrated
  27. distillationDistillation of the residual oil through a 6 cm

Sources & evidence

ORD record
ord-4d57137a38a94e608ea9af686d219f1d
Source dataset
uspto-grants-1978_03
Patent number
US04077959

Reaction notes

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