Lithium Hexamethyldisilazide → N-(2,4-Dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

HRID 46348

Reaction equation

HRID 46348 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[Si](C)(C)[N-][Si](C)(C)C.[Li+].[F:28][C:29]1[CH:34]=[C:33]([F:35])[C:32]([F:36])=[CH:31][C:30]=1[S:37](Cl)(=[O:39])=[O:38]>O1CCCC1>[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:37]([C:30]1[CH:31]=[C:32]([F:36])[C:33]([F:35])=[CH:34][C:29]=1[F:28])(=[O:39])=[O:38]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27769792,4,5-Trifluorobenzenesulfonyl chlorideHCID 57732216N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine

Product 1

HCID 59436583N-(2,4-Dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of (N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (Preparation 14, 13 g, 51.73 mmol) in dry tetrahydrofuran (150 ml) at −70° C. under argon atmosphere was added 1 M lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide in tetrahydrofuran (56.9 ml, 56.9 mmol) dropwise. The reaction mixture was allowed to warm up to room temperature and stirred for 1 h. It was again cooled to −70° C. and a tetrahydrofuran (50 ml) solution of 2,4,5-trifluorobenzenesulfonyl chloride (11.9 g, 51.73 mmol) was added dropwise to it at this temperature. After complete addition, reaction mixture was gradually allowed to warm up to room temperature and stirred for 1 hour. 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. Crude product was purified over 100-200 silica gel using 5-15% v/v ethyl acetate in hexane to give 17 g (75%) of the title compound as a white solid.

Workup

  1. temperatureIt was again cooled to −70° C.
  2. additionAfter complete addition, reaction mixture
  3. temperatureto warm up to room temperature
  4. stirringstirred for 1 hour
  5. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with water and saturated aqueous sodium chloride solution
  8. customCrude product was purified over 100-200 silica gel using 5-15% v/v ethyl acetate in hexane

Sources & evidence

ORD record
ord-a3854f3601e3420b8231e1fdd086add6
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Linked notes

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