Triethylamine → 2-Trifluoromethyl-10-[3-(4-beta-hydroxyethoxy-4-propylpiperidino)-propyl]-phenothiazine

HRID 329048

Reaction equation

HRID 329048 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:16]=[CH:15][C:14]2[S:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[N:6]([CH2:17][CH2:18][CH2:19]Cl)[C:5]=2[CH:4]=1.C(N(CC)CC)C.[CH2:30]([C:33]1([O:39][CH2:40][CH2:41][OH:42])[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)[CH2:31][CH3:32]>C(C(C)=O)C.[I-].[Na+]>[F:1][C:2]([F:22])([F:21])[C:3]1[CH:16]=[CH:15][C:14]2[S:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[N:6]([CH2:17][CH2:18][CH2:19][N:36]3[CH2:37][CH2:38][C:33]([O:39][CH2:40][CH2:41][OH:42])([CH2:30][CH2:31][CH3:32])[CH2:34][CH2:35]3)[C:5]=2[CH:4]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 7429410-(3-Chloropropyl)-2-(trifluoromethyl)-10H-phenothiazineHCID 214408792-(4-Propyl-4-piperidyloxy)-ethanol

Product 1

HCID 542643272-Trifluoromethyl-10-[3-(4-beta-hydroxyethoxy-4-propylpiperidino)-propyl]-phenothiazineYield 99.6%

Reagents, catalysts & solvents 2

HCID 5238Sodium IodideSolventHCID 6569Methyl Ethyl KetoneSolvent2×

Procedure

10 g of 2-trifluoromethyl-10-(3-chloropropyl)-phenothiazine were dissolved in 50 ml of methyl ethyl ketone and 4.36 g of sodium iodide, 2.9 g of triethylamine, then dropwise a solution of 5.4 g of 2-(4-propyl-4-piperidyloxy)-ethanol in 50 ml of methyl ethyl ketone were added successively thereto. The mixture was refluxed for 24 hours and after cooling, the precipitate formed was removed by vacuum filtration. The precipitate formed was removed by filtration and the filtrate was evaporated in vacuo and the residue was dissolved in methylene chloride. The organic solution was washed with an aqueous solution of sodium bicarbonate, then with water and the solution was dried and concentrated in vacuo to obtain 14.2 g of 2-trifluoromethyl-10-[3-(4-β-hydroxyethoxy-4-propylpiperidino)-propyl]-phenothiazine as a beige product which was dissolved in 50 ml of ethanol. The resulting solution was reacted with an ether solution of hydrogen chloride and the hydrochloride was precipitated by the addition of ether. The said precipitate was recovered by vacuum filtration and was washed with ether and crystallized from acetonitrile to obtain 7 g of 2-trifluoromethyl-10-[3-(4-β-hydroxyethoxy-4-propylpiperidino)-propyl]-phenothiazine hydrochloride as white crystals melting at 192° C.

Workup

  1. temperatureThe mixture was refluxed for 24 hours
  2. temperatureafter cooling
  3. customthe precipitate formed
  4. customwas removed by vacuum filtration
  5. customThe precipitate formed
  6. customwas removed by filtration
  7. customthe filtrate was evaporated in vacuo
  8. dissolutionthe residue was dissolved in methylene chloride
  9. washThe organic solution was washed with an aqueous solution of sodium bicarbonate
  10. dry with materialwith water and the solution was dried
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cb32354199474c3facec98c1d8c1246b
Source dataset
uspto-grants-1977_04
Patent number
US04018922

Linked notes

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