Sodium hydride → HCID 67966860, compound

HRID 2178552Notes

Reaction equation

HRID 2178552 reaction equation
[CH:1]([C:4]1[N:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]2=[N:6][C:5]=1[NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:3])[CH3:2].[H-].[Na+].Cl[S:24]([C:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=1)(=[O:26])=[O:25]>CN(C=O)C>[C:16]([O:15][C:14]([N:13]([C:5]1[N:6]=[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]2[C:4]=1[CH:1]([CH3:3])[CH3:2])[S:24]([C:27]1[CH:28]=[CH:29][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:35][CH:36]=1)(=[O:26])=[O:25])=[O:20])([CH3:18])([CH3:17])[CH3:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 4738388Methyl 4-(Chlorosulfonyl)benzoateHCID 67966865HCID 67966865, compound

Product 1

HCID 67966860HCID 67966860, compoundYield 51.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of compound 4-E (0.267 g, 0.97 mmol) in DMF (10 mL), cooled to 0° C., was added 60% NaH (0.043 g, 1.08 mmol) and the reaction mixture was stirred at 0° C. for 40 min. Methyl 4-(chlorosulfonyl)benzoate (0.341 g, 1.46 mmol) was added in one-portion and the reaction mixture was stirred at ambient temperature for 2 h. Ice water was added to the reaction solution and the product was extracted into EtOAc, washed with H2O (2×), then brine, and dried over Na2SO4, filtered, and the solvent evaporated under reduced pressure to afford a crude product. The crude material was purified by flash column chromatography (SiO2) eluting with a gradient of EtOAc (20-60%) in heptanes to afford compound 4-F as a colorless glass (0.235 g, 51%). 1H-NMR (CDCl3): δ 8.4 (d, J=8.7 Hz, 2H), 8.24 (d, J=8.7 Hz, 2H), 8.05 (d, J=7.1 Hz, 1H), 7.62 (d, J=9.0 Hz, 1H), 7.19-7.24 (m, 1H), 6.86-6.90 (m, 1H), 3.98 (s, 3H), 3.37-3.50 (m, 2H), 1.50-1.59 (m, 6H under H2O peak), 1.32 (s, 9H); MS: m/z 474.1 (MH+).

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 2 h
  2. extractionthe product was extracted into EtOAc
  3. washwashed with H2O (2×)
  4. dry with materialbrine, and dried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customto afford a crude product
  8. customThe crude material was purified by flash column chromatography (SiO2)
  9. washeluting with a gradient of EtOAc (20-60%) in heptanes

Sources & evidence

ORD record
ord-5c392501bbda4d0b9abc1e6684d46aab
Source dataset
uspto-grants-2015_06
Patent number
US09067935B2

Reaction notes

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