Phosphorus pentachloride → Etonitazene

HRID 2074445Notes

Reaction equation

HRID 2074445 reaction equation
[CH2:1]([N:3]([CH2:29][CH3:30])[CH2:4][CH2:5][NH:6][C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][C:8]=1[NH:16][C:17](=O)[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH3:27])=[CH:21][CH:20]=1)[CH3:2].P(Cl)(Cl)(Cl)(Cl)Cl>C(Cl)(Cl)Cl.O.[OH-].[NH4+]>[CH2:26]([O:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][C:17]2[N:6]([CH2:5][CH2:4][N:3]([CH2:29][CH3:30])[CH2:1][CH3:2])[C:7]3[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][C:8]=3[N:16]=2)=[CH:20][CH:21]=1)[CH3:27]

Participants

6

Reactant 2

HCID 24819Phosphorus pentachlorideHCID 4405038N-[2-(2-Diethylaminoethylamino)-5-nitro-phenyl]-2-(4-ethoxyphenyl)acetamide

Product 1

HCID 13493Etonitazene

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolvent2×HCID 14923Ammonium HydroxideSolvent

Procedure

N-[2-(2-Diethylamino-ethylamino)-5-nitro-phenyl]-2-(4-ethoxy-phenyl)-acetamide 6a (295 mg, 0.712 mmol), Phosphorous pentachloride (148.3 mg, 0.712 mmol) were dissolved in anhydrous chloroform (10 mL) in a small, argon purged flask fitted with a condenser and magnetic stirbar. The solution was heated to reflux in an oil bath for 4 hours and cooled to room temperature overnight. The mixture was diluted with H2O and chloroform and 2M ammonium hydroxide solution added to adjust pH to 9-10. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with chloroform and the combined organic layers were washed with brine, dried over magnesium sulphate, filtered and concentrated to afford crude. The product was purified using dry silica gel column chromatography eluting with 25 mL portions of solvent system (2.5% 2M NH3 in methanol/95% dichloromethane) to afford a yellow residue. Recrystallization from diethyl ether/hexanes at 0° C. yielded a pale yellow solid 7a {2-[2-(4-Ethoxy-benzyl)-5-nitro-benzoimidazol-1-yl]-ethyl}-diethyl-amine. Yield: 177 mg (62.7%). 1H NMR (DMSO) : 0.71 (t, 6H, J=7.0), 1.29 (t, 3H, J=7.0), 2.37 (q, 4H, J=7.1), 2.50 (m, 2H), 3.98 (q, 2H, J=6.9), 4.25 (m, 2H), 4.32 (s, 2H), 6.87 (d, 2H, J=8.4), 7.19 (d, 2H, J=8.4), 7.71 (d, 1H, J=8.9), 8.14 (dd, 2H, J=8.9, 2.1), 8.45 (d, 1H, J=2.1); MS (ESI): 397 (MH+, 100%)

Workup

  1. customfitted with a condenser
  2. temperatureThe solution was heated
  3. temperatureto reflux in an oil bath for 4 hours
  4. additionadded
  5. customThe mixture was transferred to a separatory funnel
  6. customthe organic layer collected
  7. extractionThe aqueous layer was further extracted with chloroform
  8. washthe combined organic layers were washed with brine
  9. dry with materialdried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford crude
  13. customThe product was purified
  14. washeluting with 25 mL portions of solvent system (2.5% 2M NH3 in methanol/95% dichloromethane)
  15. customto afford a yellow residue
  16. customRecrystallization from diethyl ether/hexanes at 0° C.

Sources & evidence

ORD record
ord-1d9aafeccb2247ccae8745bbfca7b4f0
Source dataset
uspto-grants-2011_04
Patent number
US07919510B2

Reaction notes

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