Sodium Hydroxide → 1-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-4-[2-[4-(3-phthalimidopropyloxy)phenoxy]ethyl]piperazine

HRID 2418007Notes

Reaction equation

HRID 2418007 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[S:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][N:22]([CH2:25][CH2:26]Cl)[CH2:21][CH2:20]3)[C:4]=2[CH:3]=1.[C:28]1(=[O:49])[N:32]([CH2:33][CH2:34][CH2:35][O:36][C:37]2[CH:42]=[CH:41][C:40]([OH:43])=[CH:39][CH:38]=2)[C:31](=[O:44])[C:30]2=[CH:45][CH:46]=[CH:47][CH:48]=[C:29]12.[OH-].[Na+]>CS(C)=O.O>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[S:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([CH2:16][CH2:17][CH2:18][N:19]3[CH2:20][CH2:21][N:22]([CH2:25][CH2:26][O:43][C:40]4[CH:39]=[CH:38][C:37]([O:36][CH2:35][CH2:34][CH2:33][N:32]5[C:28](=[O:49])[C:29]6=[CH:48][CH:47]=[CH:46][CH:45]=[C:30]6[C:31]5=[O:44])=[CH:42][CH:41]=4)[CH2:23][CH2:24]3)[C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 52754552-Chloro-10-[3-[4-(2-chloroethyl)piperazin-1-yl]propyl]phenothiazineHCID 133384944-(3-Phthalimidopropoxy)phenol

Product 1

HCID 133384601-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-4-[2-[4-(3-phthalimidopropyloxy)phenoxy]ethyl]piperazineYield 6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×

Procedure

To a stirred solution of 1-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-4-(2-chloroethyl) piperazine (24 g) and 14.5 g of 4-(3-phthalimidopropyloxy)phenol in dimethylsulfoxide (500 ml) at 50° under nitrogen was added sodium hydroxide (1.9 g) in water (15 ml), and the solution was stirred for 5 hours 55°-60°. After standing at room temperature overnight, the reaction was poured into water (1 L) and the oil was extracted using ethyl acetate. The extract dried over sodium sulfate was evaporated in vacuo and the residual material was dissolved in acetonitrile. The supernatant was decanted from some insoluble material and then hydrogen chloride was bubbled into the solution to precipitate the product as the dihydrochloride salt. Methanol was added to the mixture to redissolve the salt and the solution was concentrated until a solid started to precipitate. The solid was collected by filtration to give 2 g of 1-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-4-[2 -[4-(3-phthalimidopropyloxy)phenoxy]ethyl]piperazine as its di-hydrochloride salt, mp 233°-246°. The filtrate was evaporated and the resulting oil was crystallized from methanol yielding an additional 8.3 g of the same material, mp 225°-240°

Workup

  1. waitAfter standing at room temperature overnight
  2. extractionthe oil was extracted
  3. dry with materialThe extract dried over sodium sulfate
  4. customwas evaporated in vacuo
  5. dissolutionthe residual material was dissolved in acetonitrile
  6. customThe supernatant was decanted from some insoluble material
  7. customhydrogen chloride was bubbled into the solution
  8. customto precipitate the product as the dihydrochloride salt
  9. additionMethanol was added to the mixture
  10. dissolutionto redissolve the salt
  11. concentrationthe solution was concentrated until a solid
  12. customto precipitate
  13. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-2262bc851b4a44c4b9234608a2b630b5
Source dataset
uspto-grants-1984_09
Patent number
US04471116

Reaction notes

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