Diethylaminoethyl chloride → Etonitazene 6-nitro isomer

HRID 2074459Notes

Reaction equation

HRID 2074459 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]1[CH:24]=[CH:23][C:9]([CH2:10][C:11]2[NH:15][C:14]3[CH:16]=[CH:17][C:18]([N+:20]([O-:22])=[O:21])=[CH:19][C:13]=3[N:12]=2)=[CH:8][CH:7]=1)[CH3:4].Cl[CH2:26][CH2:27][N:28]([CH2:31][CH3:32])[CH2:29][CH3:30]>O1CCOCC1>[CH2:3]([O:5][C:6]1[CH:24]=[CH:23][C:9]([CH2:10][C:11]2[N:12]([CH2:26][CH2:27][N:28]([CH2:31][CH3:32])[CH2:29][CH3:30])[C:13]3[CH:19]=[C:18]([N+:20]([O-:22])=[O:21])[CH:17]=[CH:16][C:14]=3[N:15]=2)=[CH:8][CH:7]=1)[CH3:4]

Participants

5

Reactant 3

HCID 13364Diethylaminoethyl chlorideHCID 24758Sodium hydride2×HCID 178466243HCID 178466243, compound

Product 1

HCID 59799752Etonitazene 6-nitro isomerYield 13.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent3×

Conditions

Temperature
65 °C

Procedure

To a small, argon purged flask fitted with a condenser and magnetic stirbar is charged Sodium Hydride (60 wt %, 74 mg, 1.850 mmol) and anhydrous dioxane (5 mL) and stirring begun. A solution of 2-(4-Ethoxy-benzyl)-5-nitro-1H-benzimidazole 42 (550 mg, 1.850 mmol) in anhydrous dioxane (10 mL) was added dropwise to the suspension of sodium hydride and the mixture heated to 65° C. for 90 minutes at which time a solution of (2-Chloroethyl)-diethyl-amine (251 mg, 1.850 mmol) in anhydrous dioxane (5 mL) is added dropwise to the hot solution. After 60 minutes at 65° C. the mixture is cooled to room temperature, filtered and solvent removed under reduced pressure to afford crude. The product was purified using dry silica gel column chromatography eluting with 25 mL portions of solvent system (1.25% 2M NH3 in methanol/98.75% dichloromethane to 2.5% 2M NH3 in methanol/97.5% dichloromethane). The enriched fractions were further purified using silica gel column chromatography eluting with 50% ethyl acetate/50% hexanes to 70% ethyl acetate/30% hexanes to afford a pale yellow-colorless solid 43 {2-[2-(4-Ethoxy-benzyl)-6-nitro-benzoimidazol-1-yl]-ethyl}-diethyl-amine Yield: 100 mg (13.6%). 1H NMR (DMSO) δ: 0.70 (t, 6H, J=7.1), 1.30 (t, 3H, J=6.9), 2.39 (q, 4H, J=7.1), 2.50 (m, 2H), 3.98 (q, 2H, J=6.9), 4.28-4.36 (s, 2H; m, 2H) 6.87 (d, 2H, J=8.7), 7.20 (d, 2H, J=8.6), 7.72 (d, 1H, J=9.0), 8.06 (dd, 2H, J=8.9, 2.1), 8.51 (d, 1H, J=2.1); MS (ESI): 397 (MH+, 100%).

Workup

  1. customTo a small, argon purged flask fitted with a condenser
  2. additionis added dropwise to the hot solution
  3. filtrationfiltered
  4. customsolvent removed under reduced pressure
  5. customto afford crude
  6. customThe product was purified
  7. washeluting with 25 mL portions of solvent system (1.25% 2M NH3 in methanol/98.75% dichloromethane to 2.5% 2M NH3 in methanol/97.5% dichloromethane)
  8. customThe enriched fractions were further purified
  9. washeluting with 50% ethyl acetate/50% hexanes to 70% ethyl acetate/30% hexanes

Sources & evidence

ORD record
ord-6255660cac294a18915ef2769ab34b8e
Source dataset
uspto-grants-2011_04
Patent number
US07919510B2

Reaction notes

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