Triethylamine → 1,8-Diazabicyclo(5.4.0)undec-7-ene

HRID 540904Notes

Reaction equation

HRID 540904 reaction equation
Cl[CH2:2][CH2:3][CH2:4][S:5](Cl)(=[O:7])=[O:6].Cl.Cl.[CH2:11]([O:18][C:19]1[CH:20]=[CH:21][C:22]2[C:23]3[N:31]([CH2:32][CH2:33][CH2:34][CH2:35][NH2:36])[C:30]([CH2:37][O:38][CH2:39][CH3:40])=[N:29][C:24]=3[CH:25]=[N:26][C:27]=2[CH:28]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C.[N:48]12[CH2:58][CH2:57][CH2:56][N:55]=[C:54]1[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]2>ClCCl>[CH2:11]([O:18][C:19]1[CH:20]=[CH:21][C:22]2[C:23]3[N:31]([CH2:32][CH2:33][CH2:34][CH2:35][N:36]4[CH2:2][CH2:3][CH2:4][S:5]4(=[O:7])=[O:6])[C:30]([CH2:37][O:38][CH2:39][CH3:40])=[N:29][C:24]=3[CH:25]=[N:26][C:27]=2[CH:28]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[N:48]12[CH2:58][CH2:57][CH2:56][N:55]=[C:54]1[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 154103-Chloropropanesulphonyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 67051132HCID 67051132, compound

Product 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 67051030HCID 67051030, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Chloropropanesulfonyl chloride (4.58 mL, 37.7 mmol) was added dropwise to a solution of 4-[7-(benzyloxy)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butan-1-amine dihydrochloride (12.1 g, 25.3 mmol) and triethylamine (14.0 mL, 101 mmol) in dichloromethane (168 mL) at room temperature. The solution was stirred for 17 hours, then transferred to a separatory funnel and washed with 5% aqueous sodium carbonate, water, and saturated aqueous sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in DMF (168 mL) and treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (5.70 mL, 38 mmol). The solution was stirred for 40 hours, then the DMF was removed under reduced pressure. The residue was dissolved in dichloromethane and washed repeatedly with water then saturated aqueous sodium carbonate. The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated to afford 7-(benzyloxy)-1-[4-(1,1-dioxidoisothiazolidin-2-yl)butyl]-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinoline in almost quantitative yield with some residual 1,8-diazabicyclo[5.4.0]undec-7-ene as a brown oil, which was used without further purification.

Workup

  1. customtransferred to a separatory funnel
  2. washwashed with 5% aqueous sodium carbonate, water, and saturated aqueous sodium chloride
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in DMF (168 mL)
  7. stirringThe solution was stirred for 40 hours
  8. customthe DMF was removed under reduced pressure
  9. dissolutionThe residue was dissolved in dichloromethane
  10. washwashed repeatedly with water
  11. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-57eea1d8f45446febd70641c746decf0
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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