Water → Ethyl 4-(4-(methylsulfonyl)phenoxy)-2-((2-oxopyrrolidin-1-yl)methyl)benzofuran-6-carboxylate

HRID 1643761Notes

Reaction equation

HRID 1643761 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][NH:3]1.[H-].[Na+].Br[CH2:10][C:11]1[O:12][C:13]2[CH:19]=[C:18]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:17]=[C:16]([O:25][C:26]3[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][CH:27]=3)[C:14]=2[CH:15]=1.O>CN(C=O)C>[CH3:35][S:32]([C:29]1[CH:30]=[CH:31][C:26]([O:25][C:16]2[C:14]3[CH:15]=[C:11]([CH2:10][N:3]4[CH2:4][CH2:5][CH2:6][C:2]4=[O:1])[O:12][C:13]=3[CH:19]=[C:18]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:17]=2)=[CH:27][CH:28]=1)(=[O:34])=[O:33]

Participants

6

Reactant 4

HCID 962WaterHCID 120252-PyrrolidoneHCID 24758Sodium hydrideHCID 66755908Ethyl 2-(bromomethyl)-4-(4-(methylsulfonyl)phenoxy)benzofuran-6-carboxylate

Product 1

HCID 66755917Ethyl 4-(4-(methylsulfonyl)phenoxy)-2-((2-oxopyrrolidin-1-yl)methyl)benzofuran-6-carboxylateYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-ketopyrrolidine (75.1 mg, 0.882 mmol) in DMF (10 mL) was added NaH (60% in mineral oil, 44 mg, 1.1 mmol) at room temperature. After stirring the reaction for 30 min, ethyl 2-(bromomethyl)-4-(4-(methylsulfonyl)phenoxy)benzofuran-6-carboxylate (285a) (200 mg, 0.441 mmol) was added. The mixture was stirred at room temperature for another 2 h. Water was added to the reaction, and the product was extracted with CHCl3. The combined organic layer was dried and concentrated. The product was purified by gradient silica gel chromatography using CHCl3/MeOH (100/0 to 95/5) to give the title compound (50 mg, 25%) as a yellow oil. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.38 (t, J=7.16 Hz, 3 H) 1.98-2.14 (m, 2 H) 2.42 (t, J=8.10 Hz, 2 H) 3.06 (s, 3 H) 3.44 (t, J=7.06 Hz, 2 H) 4.38 (q, J=7.16 Hz, 2 H) 4.58 (s, 2 H) 6.49 (d, J=0.75 Hz, 1 H) 7.04-7.12 (m, 2 H) 7.61 (d, J=1.13 Hz, 1 H) 7.83-7.94 (m, 2 H) 8.05 (t, J=1.13 Hz, 1 H).

Workup

  1. customthe reaction for 30 min
  2. stirringThe mixture was stirred at room temperature for another 2 h
  3. extractionthe product was extracted with CHCl3
  4. customThe combined organic layer was dried
  5. concentrationconcentrated
  6. customThe product was purified by gradient silica gel chromatography

Sources & evidence

ORD record
ord-6aae80fab88243bea0949cdff9493542
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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