Imidazole → HCID 131731316, compound

HRID 2364970Notes

Reaction equation

HRID 2364970 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][NH:5][CH:6]=1.N1[CH:11]=[CH:10][N:9]=C1.ClN1[C:17](=O)[CH2:16][CH2:15][C:14]1=[O:19].[OH2:20].CN(C)C=[O:24]>>[ClH:1].[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:17]2[CH:16]=[C:15]([C:14]([OH:19])=[O:24])[NH:9][C:10](=[O:20])[CH:11]=2)[CH:6]=1

Participants

6

Reactant 5

HCID 795ImidazoleHCID 962WaterHCID 6228Dimethylformamide2×HCID 31398ChlorosuccinimideHCID 178478287HCID 178478287, compound

Product 1

HCID 131731316HCID 131731316, compound

Procedure

Synthesis of 4-chloro-1H-imidazole (C33). To a solution of 1H-imidazole (22.1 g, 324 mmol) in N,N-dimethylformamide at 0° C. was added drop-wise (over 4 hours) a solution of N-chlorosuccinimide (25 g, 190 mmol) in N,N-dimethylformamide (total solvent, 160 mL). The reaction was stirred at 0° C. for 1 hour, whereupon water (200 mL) was added at 0° C. The mixture was extracted with ethyl acetate (3×50 mL), and the combined organic layers were concentrated in vacuo. Purification was carried out using supercritical fluid chromatography (Column: Princeton Cyano, 5 μm; Eluant: 15:85 methanol/carbon dioxide). The resulting material was purified again, using silica gel chromatography (Mobile phase A: ethyl acetate; Mobile phase B: [20% (2 M ammonia in methanol) in dichloromethane]; Gradient: 0% to 10% B) to afford the title compound as a white solid. Yield: 2.45 g, 23.9 mmol, 12%. GCMS m/z 102, 104 (M+). 1H NMR (400 MHz, CDCl3) δ 7.00 (d, J=1.2 Hz, 1H), 7.57 (br s, 1H), 11.3 (v br s, 1H).

Workup

  1. additionwas added at 0° C
  2. extractionThe mixture was extracted with ethyl acetate (3×50 mL)
  3. concentrationthe combined organic layers were concentrated in vacuo
  4. customPurification
  5. customThe resulting material was purified again

Sources & evidence

ORD record
ord-8afaf3bf85654e1991f950010728801e
Source dataset
uspto-grants-2014_04
Patent number
US08697673B2

Reaction notes

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