Sodium hydride → N-(3-acetyl-benzo[b]thiophen-2-yl)-N-(4-fluoro-3-trifluoromethyl-benzyl)-ethanesulfonamide

HRID 1511501Notes

Reaction equation

HRID 1511501 reaction equation
[H-].[Na+].[C:3]([C:6]1[C:7]2[CH:20]=[CH:19][CH:18]=[CH:17][C:8]=2[S:9][C:10]=1[NH:11][S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])(=[O:5])[CH3:4].[F:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26]Br)=[CH:24][C:23]=1[C:30]([F:33])([F:32])[F:31].C1OCCOCCOCCOCCOC1>CN(C=O)C.O>[C:3]([C:6]1[C:7]2[CH:20]=[CH:19][CH:18]=[CH:17][C:8]=2[S:9][C:10]=1[N:11]([CH2:26][C:25]1[CH:28]=[CH:29][C:22]([F:21])=[C:23]([C:30]([F:33])([F:31])[F:32])[CH:24]=1)[S:12]([CH2:15][CH3:16])(=[O:13])=[O:14])(=[O:5])[CH3:4]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 27375774-Fluoro-3-(trifluoromethyl)benzyl bromide2×HCID 57920498N-(3-acetyl-benzo[b]thiophen-2-yl)-ethanesulfonamide

Product 1

HCID 57920447N-(3-acetyl-benzo[b]thiophen-2-yl)-N-(4-fluoro-3-trifluoromethyl-benzyl)-ethanesulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% in oil, 46 mg, 1.15 mmol) was added to a solution of N-(3-acetyl-benzo[b]thiophen-2-yl)-ethanesulfonamide (310 mg, 1.09 mmol) in DMF (4 mL), at 0° C. The resulting mixture was stirred at 0° C. for 15 min, to which was added 4-fluoro-3-trifluoromethylbenzyl bromide (253 μL, 1.33 mmol) and the resulting mixture stirred at ambient temperature for 2 h. 15-Crown-5 ether (220 μL, 1.33 mmol) and an additional equivalent of 4-fluoro-3-trifluoromethylbenzyl bromide was then added. The resulting solution was stirred at ambient temperature overnight, water was then added, and the desired product extracted into ethyl acetate. The organic phase was washed with water (3×), brine, dried over sodium sulfate, filtered, and the solvent evaporated in vacuo to yield a residue. The residue was purified by flash column chromatography (SiO2), eluting with an ethyl acetate-heptane gradient to yield N-(3-acetyl-benzo[b]thiophen-2-yl)-N-(4-fluoro-3-trifluoromethyl-benzyl)-ethanesulfonamide as an off-white solid. 1H-NMR (DMSO-d6): δ 1.32 (t, 3H), 2.29 (s, 3H), 3.49 (q, 2H), 5.08 (s, 2H), 7.41-7.52 9m, 3H), 7.70-7.77 (m, 2H), 7.93-8.03 (m, 2H); MS: m/z 460.2 (MH+).

Workup

  1. stirringthe resulting mixture stirred at ambient temperature for 2 h
  2. stirringThe resulting solution was stirred at ambient temperature overnight
  3. extractionthe desired product extracted into ethyl acetate
  4. washThe organic phase was washed with water (3×), brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent evaporated in vacuo
  8. customto yield a residue
  9. customThe residue was purified by flash column chromatography (SiO2)
  10. washeluting with an ethyl acetate-heptane gradient

Sources & evidence

ORD record
ord-7dab926527da4afd88fcb9cd95268c6c
Source dataset
uspto-grants-2012_07
Patent number
US08216547B2

Reaction notes

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