Chlorambucil → HCID 15634255, compound

HRID 1458707Notes

Reaction equation

HRID 1458707 reaction equation
[CH:1]1[C:6]([CH2:7][CH2:8][CH2:9]C(O)=O)=[CH:5][CH:4]=[C:3]([N:13]([CH2:17][CH2:18][Cl:19])[CH2:14][CH2:15][Cl:16])[CH:2]=1.C([N:22](CC)CC)C.ClC(OCC)=O.[N-]=[N+]=[N-].[Na+]>CC(C)=O.O>[Cl:16][CH2:15][CH2:14][N:13]([C:3]1[CH:4]=[CH:5][C:6]([CH2:7][CH2:8][CH2:9][NH2:22])=[CH:1][CH:2]=1)[CH2:17][CH2:18][Cl:19]

Participants

7

Reactant 4

HCID 2708ChlorambucilHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 33557Sodium Azide

Product 1

HCID 15634255HCID 15634255, compoundYield 77.1%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Chlorambucil (0.30 g; 0.99 mmol) was suspended in 2 ml of acetone. The resultant mixture was stirred under a nitrogen gas atmosphere and ice-cooling, to which 0.17 ml (1.22 mmol; 1.2 equivalents) of triethylamine and 0.11 ml (1.22 mmol; 1.2 equivalents) of ethyl chloroformate were added successively. Twenty minutes later, a solution of 0.13 g (2.0 mmol; 2.0 equivalents) of sodium azide in 2 ml of water was added dropwise. The resulting mixture was stirred, as was, for 1 hour, to which ice was added to terminate the reaction. The thus-obtained mixture was extracted three times with 20 ml portions of benzene. The benzene layers were combined, dried over sodium sulfate and then heated under reflux for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was added with 9 ml of 8N hydrochloric acid, followed by heating for 15 minutes at 100° C. The resulting mixture was concentrated under reduced pressure and the residue was diluted with water. The thus-obtained mixture was adjusted to pH 12 with concentrated aqueous ammonia, followed by extraction with ethyl acetate. The extract was dried and concentrated, whereby 0.21 g of the title compound was obtained as a crude yellow oil of high viscosity. This reaction product was provided for use in the next reaction without purification.

Workup

  1. additionwere added successively
  2. additionwas added
  3. customto terminate
  4. customthe reaction
  5. extractionThe thus-obtained mixture was extracted three times with 20 ml portions of benzene
  6. dry with materialdried over sodium sulfate
  7. temperatureheated
  8. temperatureunder reflux for 1 hour
  9. concentrationThe reaction mixture was concentrated under reduced pressure
  10. additionThe residue was added with 9 ml of 8N hydrochloric acid
  11. concentrationThe resulting mixture was concentrated under reduced pressure
  12. additionthe residue was diluted with water
  13. extractionfollowed by extraction with ethyl acetate
  14. customThe extract was dried
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-18bfd845e7e748ba8802877158ce610f
Source dataset
uspto-grants-1998_12
Patent number
US05852011

Reaction notes

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