Hydrochloric Acid → BendaMustine IMpurity C

HRID 2407390Notes

Reaction equation

HRID 2407390 reaction equation
[CH3:1][N:2]1[C:10]([CH2:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15])=[N:9][C:8]2[CH:7]=[C:6]([N:17]([CH2:21][CH2:22][Cl:23])[CH2:18][CH2:19][Cl:20])[CH:5]=[CH:4][C:3]1=2.Cl.Cl.C(=O)(O)[O-].[K+].[CH:31](O)([CH3:33])[CH3:32]>O>[CH3:32][CH:31]([O:15][C:14]([CH2:13][CH2:12][CH2:11][C:10]1[N:2]([CH3:1])[C:3]2[CH:4]=[CH:5][C:6]([N:17]([CH2:18][CH2:19][Cl:20])[CH2:21][CH2:22][Cl:23])=[CH:7][C:8]=2[N:9]=1)=[O:16])[CH3:33]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 77082Bendamustine HydrochlorideHCID 516893Potassium Bicarbonate

Product 1

HCID 53258886BendaMustine IMpurity C

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

Bendamustine HCl×H2O (1 g, 2.83 mmol) was suspended iso-propanol (5 mL). Hydrochloric acid (0.3 mL; 8N in iso-propanol) was added and the stirred mixture was heated to reflux temperature for 5 h. After that the product solution was added to potassium bicarbonate (0.6 g) in RO-water (50 mL); final pH value was between 7 and 8. An oil forms. The emulsion was extracted twice with ethyl acetate (30+20 mL), the combined organic extracts were dried over sodium sulphate and concentrated under reduced pressure with a rotary evaporator (0.9 g, crystalline, crude material). The solid was slurried with methyl-tertiary butyl-ether (5 mL), isolated by filtration, washed with cold methyl-tertiary butyl-ether (2×0.8 mL) and dried in the fumehood. Yield: 0.47 g.

Workup

  1. temperaturethe stirred mixture was heated
  2. temperatureto reflux temperature for 5 h
  3. extractionThe emulsion was extracted twice with ethyl acetate (30+20 mL)
  4. dry with materialthe combined organic extracts were dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure with a rotary evaporator (0.9 g, crystalline, crude material)
  6. customisolated by filtration
  7. washwashed with cold methyl-tertiary butyl-ether (2×0.8 mL)
  8. customdried in the fumehood

Sources & evidence

ORD record
ord-cdcd930274a744c5a37adb44fb21b94d
Source dataset
uspto-grants-2014_08
Patent number
US08809549B2

Reaction notes

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