2-(2-Acetamino-phenylsulfanyl)-phenyl-{4(2-(2-acetoxyethoxy)ethyl]piperazin-1-yl}methanone → Quetiapine acetate

HRID 251396Notes

Reaction equation

HRID 251396 reaction equation
[NH:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]([N:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][O:28][CH2:29][CH2:30][O:31][C:32](=[O:34])[CH3:33])[CH2:22][CH2:21]1)=O)C(C)=O>O=P(Cl)(Cl)Cl>[C:32]([O:31][CH2:30][CH2:29][O:28][CH2:27][CH2:26][N:23]1[CH2:24][CH2:25][N:20]([C:18]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[S:11][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[N:1]=2)[CH2:21][CH2:22]1)(=[O:34])[CH3:33]

Participants

3

Reactant 1

HCID 111559842-(2-Acetamino-phenylsulfanyl)-phenyl-{4(2-(2-acetoxyethoxy)ethyl]piperazin-1-yl}methanone

Product 1

HCID 11487114Quetiapine acetateYield 87.7%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

[2-(2-acetamino-phenylsulfanyl)-phenyl-{4(2-(2-acetoxyethoxy)ethyl]piperazin-1-yl}methanone (2 g, 0.0041 mol) was dissolved in POCl3 (5 ml) and stirred at room temperature for 30 min. The mixture was slowly heated to reflux and refluxed for 3 h. Excess of POCl3 was evaporated and water 50 ml and methanol (5 ml) were carefully added to the residue. The mixture was stirred at room temperature until all material was dissolved. The pH of the water was adjusted to 10-11 by addition of NaOH followed by extraction with toluene 2×50 ml. The organic layer was separated and evaporated to give a dark residue of 11-(4-[2-(2-acetyloxy-ethoxy)ethyl]-1-piperazinyl]dibenzo[b,f]-1,4-thiazepine (1.53 g).

Workup

  1. temperatureThe mixture was slowly heated
  2. temperatureto reflux
  3. temperaturerefluxed for 3 h
  4. customExcess of POCl3 was evaporated
  5. additionwater 50 ml and methanol (5 ml) were carefully added to the residue
  6. stirringThe mixture was stirred at room temperature until all material
  7. dissolutionwas dissolved
  8. additionThe pH of the water was adjusted to 10-11 by addition of NaOH
  9. extractionfollowed by extraction with toluene 2×50 ml
  10. customThe organic layer was separated
  11. customevaporated

Sources & evidence

ORD record
ord-10de0e47ae9744cd9a55de7547545e77
Source dataset
uspto-grants-2011_01
Patent number
US07863441B2

Reaction notes

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