Lithium Hexamethyldisilazide → tert-Butyl 1,3-thiazol-4-yl[(2,4,5-trifluorophenyl)sulfonyl]carbamate

HRID 2283659Notes

Reaction equation

HRID 2283659 reaction equation
[S:1]1[CH:5]=[C:4]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[N:3]=[CH:2]1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[F:24][C:25]1[CH:30]=[C:29]([F:31])[C:28]([F:32])=[CH:27][C:26]=1[S:33](Cl)(=[O:35])=[O:34]>O1CCCC1>[S:1]1[CH:5]=[C:4]([N:6]([S:33]([C:26]2[CH:27]=[C:28]([F:32])[C:29]([F:31])=[CH:30][C:25]=2[F:24])(=[O:35])=[O:34])[C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])[N:3]=[CH:2]1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27769792,4,5-Trifluorobenzenesulfonyl chlorideHCID 53241636tert-butyl N-(1,3-thiazol-4-yl)carbamate

Product 1

HCID 59436528tert-Butyl 1,3-thiazol-4-yl[(2,4,5-trifluorophenyl)sulfonyl]carbamateYield 64.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl 1,3-thiazol-4-ylcarbamate (Preparation 3, 28.94 g, 145 mmol) in anhydrous tetrahydrofuran (600 mL) at −70° C., under an atmosphere of nitrogen was added lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1 M in tetrahydrofuran, 145 mL, 145 mmol) drop-wise. The reaction mixture was allowed to warm to ambient temperature and stirred for 1 hour before cooling to −70° C. once again. A solution of 2, 4,5-trifluoro benzenesulfonyl chloride (40 g, 173 mmol) in tetrahydrofuran (80 mL) was added drop-wise and then the reaction mixture was slowly warmed to ambient temperature and stirred for 2 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride solution before concentrating in vacuo. The crude residue was purified by silica gel column chromatography (0% to 15% ethyl acetate in hexanes gradient elution) to afford the title compound as white solid (37 g, 64%).

Workup

  1. temperaturebefore cooling to −70° C. once again
  2. temperaturethe reaction mixture was slowly warmed to ambient temperature
  3. stirringstirred for 2 hours
  4. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with water and saturated aqueous sodium chloride solution
  7. concentrationbefore concentrating in vacuo
  8. customThe crude residue was purified by silica gel column chromatography (0% to 15% ethyl acetate in hexanes gradient elution)

Sources & evidence

ORD record
ord-9c8662cdb8ec4e069e42a7bea4f02934
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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