Iodoethane → 1-{4-[(1-ethyl-1H-benzo[d]imidazol-2-yl)methyl]benzoyl}pyrrolidin-3-yl methanesulfonate

HRID 1163088Notes

Reaction equation

HRID 1163088 reaction equation
[CH3:1][S:2]([O:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11](=[O:28])[C:12]2[CH:17]=[CH:16][C:15]([CH2:18][C:19]3[NH:23][C:22]4[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=4[N:20]=3)=[CH:14][CH:13]=2)[CH2:7]1)(=[O:4])=[O:3].C(=O)([O-])[O-].[K+].[K+].[CH2:35](I)[CH3:36]>CN(C=O)C>[CH3:1][S:2]([O:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11](=[O:28])[C:12]2[CH:17]=[CH:16][C:15]([CH2:18][C:19]3[N:20]([CH2:35][CH3:36])[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[N:23]=3)=[CH:14][CH:13]=2)[CH2:7]1)(=[O:4])=[O:3]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 866152161-(4-((1H-Benzo[d]imidazol-2-yl)methyl)benzoyl)pyrrolidin-3-yl Methanesulfonate

Product 1

HCID 866152171-{4-[(1-ethyl-1H-benzo[d]imidazol-2-yl)methyl]benzoyl}pyrrolidin-3-yl methanesulfonateYield 19%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-5 °C

Procedure

A stirred solution of 1-{4-[(1H-benzo[d]imidazol-2-yl)methyl]benzoyl}-pyrrolidin-3-yl methanesulfonate (0.250 g, 0.6 mmol) in DMF was treated with potassium carbonate (0.260 g, 1.9 mmol), cooled to −5° C., treated dropwise with ethyl iodide (0.24 g, 1.5 mmol) at 0° C. over 20 min, warmed to room temperature, heated at 50° C. for 3 h, cooled to room temperature and filtered. The filtrate was concentrated in vacuo. The resultant residue was dissolved in ethyl acetate, washed with water, dried over sodium sulfate and concentrated in vacuo. Purification of this residue by column chromatography (neutral alumina, chloroform:methanol 100:0→98:2) afforded 1-{4-[(1-ethyl-1H-benzo[d]imidazol-2-yl)methyl]benzoyl}pyrrolidin-3-yl methanesulfonate (19%). 1H NMR (400 MHz, CDCl3): 7.79-7.77 (m, 1H), 7.44-7.51 (m, 3H), 7.32-7.25 (m, 4H), 5.37 & 5.23 (bs, 1H), 4.36 (s, 2H), 4.05-4.10 (q, J=8 Hz, 2H), 3.93 (bs, 1H), 3.82 (m, 1H), 3.57-3.71 (bs, 2H), 3.08 & 3.00 (s, 3H), 2.33-2.36 (m, 1H), 2.17-2.21 (m, 1H), 1.18-1.22 (t, J=8 Hz, 3H). [M+H] 428.

Workup

  1. temperaturewarmed to room temperature
  2. temperatureheated at 50° C. for 3 h
  3. temperaturecooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. dissolutionThe resultant residue was dissolved in ethyl acetate
  7. washwashed with water
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customPurification of this residue by column chromatography (neutral alumina, chloroform:methanol 100:0→98:2)

Sources & evidence

ORD record
ord-258b0575af254d32bd83840fe68e18e2
Source dataset
uspto-grants-2010_10
Patent number
US07820825B2

Reaction notes

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