Carbon Dioxide → N-(2,4-dimethoxybenzyl)-4-fluoro-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

HRID 1524399Notes

Reaction equation

HRID 1524399 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:11][N:10]=[CH:9][N:8]=1.C(=O)=O.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:31][C:32]1[CH:37]=[CH:36][C:35]([S:38](Cl)(=[O:40])=[O:39])=[CH:34][C:33]=1[N+:42]([O-:44])=[O:43]>C1COCC1.O.CC(C)=O>[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][N:6]([C:7]1[S:11][N:10]=[CH:9][N:8]=1)[S:38]([C:35]1[CH:36]=[CH:37][C:32]([F:31])=[C:33]([N+:42]([O-:44])=[O:43])[CH:34]=1)(=[O:39])=[O:40]

Participants

8

Reactant 4

HCID 280Carbon DioxideHCID 2733832Lithium HexamethyldisilazideHCID 27827994-Fluoro-3-nitrobenzene-1-sulfonyl chlorideHCID 57732216N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine

Product 1

HCID 71259496N-(2,4-dimethoxybenzyl)-4-fluoro-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideYield 54.2%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A round-bottom flask was charged with N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (851 mg, 3.39 mmol) and THF (10 mL) to give a clear, light yellow solution. The flask was cooled in a dry ice and acetone bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (3387 μl, 3.39 mmol) was added dropwise over 1 minute to give a suspension. The flask was removed from the cooling bath for 10 min, then re-cooled for 5 min. A solution of 4-fluoro-3-nitrobenzene-1-sulfonyl chloride (737.72 mg, 3.08 mmol) in THF (3 mL with a 1 mL flask/syringe wash) was added dropwise over 2 min. The mixture was stirred for another 5 min, then the mixture was warmed to room temperature. The reaction mixture was diluted with water and extracted with EtOAc (3×). The combined organic extract was dried over sodium sulfate, filtered and concentrated. The crude product was purified by chromatography on silica gel (0 to 30% EtOAc/heptane) to give N-(2,4-dimethoxybenzyl)-4-fluoro-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (758 mg, 1.668 mmol, 54.2% yield) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ=8.24 (s, 1 H), 8.18 (dd, J=2.4, 6.7 Hz, 1 H), 7.99 (ddd, J=2.4, 3.9, 8.8 Hz, 1 H), 7.33-7.28 (m, 1 H), 7.09 (d, J=8.4 Hz, 1 H), 6.32 (dd, J=2.3, 8.4 Hz, 1 H), 6.21 (d, J=2.4 Hz, 1 H), 5.37 (s, 2 H), 3.76 (s, 3 H), 3.63 (s, 3 H). m/z (ESI) 477.0 (M+H)+.

Workup

  1. customto give a clear, light yellow solution
  2. customto give a suspension
  3. customThe flask was removed from the cooling bath for 10 min
  4. temperaturere-cooled for 5 min
  5. extractionextracted with EtOAc (3×)
  6. extractionThe combined organic extract
  7. dry with materialwas dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by chromatography on silica gel (0 to 30% EtOAc/heptane)

Sources & evidence

ORD record
ord-9a8594faf1b34e558bcfbe72b74d5be0
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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