Hexamethylphosphoramide → HCID 13135947, compound

HRID 2290442Notes

Reaction equation

HRID 2290442 reaction equation
CN(P(N(C)C)(N(C)C)=O)C.N1(C2C=CC(C(OCC)=O)=CC=2)CCNCC1.S(C1C=CC(C)=CC=1)([O-])(=O)=O.Cl.[O:41]([CH:48]([CH3:67])[CH2:49][N:50]1[CH2:55][CH2:54][N:53]([C:56]2[CH:66]=[CH:65][C:59]([C:60]([O:62][CH2:63][CH3:64])=[O:61])=[CH:58][CH:57]=2)[CH2:52][CH2:51]1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>O>[O:41]([CH:48]([CH3:67])[CH2:49][N:50]1[CH2:51][CH2:52][N:53]([C:56]2[CH:57]=[CH:58][C:59]([C:60]([O:62][CH2:63][CH3:64])=[O:61])=[CH:65][CH:66]=2)[CH2:54][CH2:55]1)[C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1

Participants

6

Reactant 4

HCID 12679HexamethylphosphoramideHCID 85570p-Toluenesulfonate2×HCID 2761178Ethyl 4-(piperazin-1-yl)benzoateHCID 13135948HCID 13135948, compound

Product 1

HCID 13135947HCID 13135947, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In 60 ml. HMPT there are dissolved 17.6 g. (75 mmole) ethyl 4-(piperazin-1-yl)-benzoate and 17.28 g. (75 mmole) p-toluenesulphonic acid (2-phenoxypropyl ester) and the solution is flushed with nitrogen and kept for 12 hours at reflux temperature under nitrogen. Thereafter, a further 10 mmole of tosylate are added. The reaction mixture is maintained at reflux temperature for a further 20 hours, another 1.7 g. tosylate is added thereto and heating continued for 6 hours. The reaction mixture is then cooled, stirred into water and extracted three times with methylene chloride. The combined organic phases are washed with water, dried with anhydrous magnesium sulphate and mixed with hydrogen chloride-containing ether. After evaporation, the residue crystallises to give 11.4 g. (34% of theory) of product which, after recrystallisation from ethanol/diethyl ether (1:3 v/v) gives 8.1 g. (24% of theory) ethyl 4-[1-(2-phenoxypropyl)-piperazin-4-yl]-benzoate hydrochloride; m.p. 200°-202° C.

Workup

  1. temperatureat reflux temperature under nitrogen
  2. temperatureThe reaction mixture is maintained
  3. temperatureat reflux temperature for a further 20 hours
  4. temperatureheating
  5. waitcontinued for 6 hours
  6. temperatureThe reaction mixture is then cooled
  7. extractionextracted three times with methylene chloride
  8. washThe combined organic phases are washed with water
  9. dry with materialdried with anhydrous magnesium sulphate
  10. additionmixed with hydrogen chloride-
  11. additioncontaining ether
  12. customAfter evaporation
  13. customthe residue crystallises
  14. customto give 11.4 g
  15. custom(34% of theory) of product which, after recrystallisation from ethanol/diethyl ether (1:3 v/v)
  16. customgives 8.1 g

Sources & evidence

ORD record
ord-c252bdfe6d114c17bc581dd6d7c2bd7c
Source dataset
uspto-grants-1986_10
Patent number
US04616086

Reaction notes

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