Lithium Hexamethyldisilazide → Ethyl 4-{[(2,4-dimethoxybenzyl)(1,3-thiazol-2-yl)amino]sulfonyl}-3-fluorobenzoate

HRID 1808256Notes

Reaction equation

HRID 1808256 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:8][CH:9]=[CH:10][N:11]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH2:28]([O:30][C:31](=[O:43])[C:32]1[CH:37]=[CH:36][C:35]([S:38](Cl)(=[O:40])=[O:39])=[C:34]([F:42])[CH:33]=1)[CH3:29]>C1COCC1>[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:8][CH:9]=[CH:10][N:11]=1)[S:38]([C:35]1[CH:36]=[CH:37][C:32]([C:31]([O:30][CH2:28][CH3:29])=[O:43])=[CH:33][C:34]=1[F:42])(=[O:39])=[O:40]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 49931979N-(2,4-dimethoxybenzyl)thiazol-2-amineHCID 57732037Ethyl 4-(chlorosulfonyl)-3-fluorobenzoate

Product 1

HCID 57731925Ethyl 4-{[(2,4-dimethoxybenzyl)(1,3-thiazol-2-yl)amino]sulfonyl}-3-fluorobenzoateYield 49.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

(2,4-Dimethoxy-benzyl)-thiazol-2-yl-amine (576 mg, 2.30 mmol) was dissolved in THF (7 mL, 80 mmol) and cooled in an ice bath. 1.0 M of lithium hexamethyldisilazide in THF (2.5 mL) was added dropwise to the reaction. After 30 minutes, a solution of 4-chlorosulfonyl-3-fluoro-benzoic acid ethyl ester (559 mg, 2.10 mmol) in THF (5 mL, 60 mmol) was added dropwise to the reaction. The reaction was stirred overnight then quenched with 20 mL saturated aqueous ammonium chloride. The aqueous phase was extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on the Isco (80 g SiO2 cartridge, 60 mL/min, hexanes to ethyl acetate) to afford the product as an orange oil (496 mg, 44%).

Workup

  1. temperaturecooled in an ice bath
  2. customthen quenched with 20 mL saturated aqueous ammonium chloride
  3. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on the Isco (80 g SiO2 cartridge, 60 mL/min, hexanes to ethyl acetate)

Sources & evidence

ORD record
ord-875c082881b349b2acc771de806bb15e
Source dataset
uspto-grants-2013_01
Patent number
US08357711B2

Reaction notes

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