Triethylamine → 4-(2,5-difluorophenyl)-1-(methylsulfonyl)-2-phenyl-2,5-dihydro-1H-pyrrole

HRID 1394917Notes

Reaction equation

HRID 1394917 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[F:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[C:14]1[CH2:18][NH:17][CH:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:15]=1.C(N(CC)CC)C>ClCCl>[F:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[C:14]1[CH2:18][N:17]([S:2]([CH3:1])(=[O:4])=[O:3])[CH:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:15]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 590017764-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole

Product 1

HCID 102463344-(2,5-difluorophenyl)-1-(methylsulfonyl)-2-phenyl-2,5-dihydro-1H-pyrrole

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (40 μL, 0.51 mmol, 1.00 equiv) was added to a solution of 4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole (2-4, 130 mg, 0.505 mmol, 1 equiv) and triethylamine (350 μL, 2.52 mmol, 5.00 equiv) in dichloromethane (30 mL) at 23° C., and the resulting reaction mixture was stirred for 16 hours. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate (3×50 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present) to provide 4-(2,5-difluorophenyl)-1-(methylsulfonyl)-2-phenyl-2,5-dihydro-1H-pyrrole (6-1) as a tan solid. 1H NMR (300 MHz, CDCl3) δ 7.39-7.30 (m, 5H), 7.09 (td, 1H, J=9.8, 4.6 Hz), 7.01 (m, 2H), 6.36 (br s, 1H), 5.76 (m, 1H), 4.84 (br d, 1H, J=13.2 Hz), 4.64 (ddd, 1H, J=13.2, 5.6, 2.0 Hz), 2.55 (s, 3H). LRMS m/z (M+H) 336.0 found, 336.1 required.

Workup

  1. customthe resulting reaction mixture
  2. customThe reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate (3×50 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present)

Sources & evidence

ORD record
ord-121f8c5aa65844d6be6b123029bf956b
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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