Nitrogen mustard hydrochloride → HCID 22414566, compound

HRID 1721310Notes

Reaction equation

HRID 1721310 reaction equation
Cl.[Cl:2][CH2:3][CH2:4][N:5]([CH2:7][CH2:8]Cl)[CH3:6].[NH2:10][C:11]1[CH:12]=[C:13]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[C:14]([O:16][CH3:17])=[O:15].C(=O)([O-])[O-].[Na+].[Na+]>C(O)CCC.O>[ClH:2].[CH3:22][O:21][C:20]1[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11]=1[N:10]1[CH2:8][CH2:7][N:5]([CH3:6])[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 5935Nitrogen mustard hydrochlorideHCID 10340Sodium CarbonateHCID 2734814Methyl 3-Amino-4-methoxybenzoate

Product 1

HCID 22414566HCID 22414566, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 962WaterSolvent

Procedure

A suspension of 2-chloro-N-(2-chloroethyl)-N-methylethanamine hydrochloride (1.92 g) and methyl 3-amino-4-methoxybenzoate (1.81 g) in n-butanol was refluxed with stirring for 19 h. Anhydrous sodium carbonate (0.54 g) was added and refluxing continued for 8.5 h. The solvent was then removed to give an oil which was taken up in water (50 ml) and 2N hydrochloric acid (50 ml) and extracted with ethyl acetate (2×50 ml). The acid solution was then basified with sodium bicarbonate and re-extracted with ethyl acetate (3×50 ml). The extracts were dried and concentrated to a semi-solid (2.47 g) which was absorbed from System A (200:8:1) (5 ml) onto Kieselgel G (100 g). Elution with the same solvent gave starting material and minor basic impurities. Further elution with System A (100:8:1) (450 ml) gave first minor impurities and later fractions afforded the free base of the desired product as a gum (0.48 g). This was taken up in methanol (5 ml), filtered and treated with ethereal hydrogen chloride and diluted to 25 ml with ethyl acetate. A cream coloured solid separated, was filtered and the solid (0.586 g) recrystallised from methanol:ethyl acetate to give the title compound m.p. 202°-204° C.

Workup

  1. temperaturewas refluxed
  2. temperaturerefluxing
  3. waitcontinued for 8.5 h
  4. customThe solvent was then removed
  5. customto give an oil which
  6. extraction2N hydrochloric acid (50 ml) and extracted with ethyl acetate (2×50 ml)
  7. extractionre-extracted with ethyl acetate (3×50 ml)
  8. customThe extracts were dried
  9. concentrationconcentrated to a semi-solid (2.47 g) which
  10. customwas absorbed from System A (200:8:1) (5 ml) onto Kieselgel G (100 g)
  11. washElution with the same solvent
  12. customgave
  13. washFurther elution with System A (100:8:1) (450 ml)
  14. customgave first minor impurities and later fractions

Sources & evidence

ORD record
ord-be88eb0da2d845e7bce0f71830633aa6
Source dataset
uspto-grants-1996_04
Patent number
US05510350

Reaction notes

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