Lithium Hexamethyldisilazide → HCID 89545477, compound

HRID 2203457Notes

Reaction equation

HRID 2203457 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]([N-][Si](C)(C)C)(C)C.[Li+].[F:28][C:29]1[C:34]([F:35])=[C:33]([F:36])[CH:32]=[CH:31][C:30]=1[S:37](Cl)(=[O:39])=[O:38]>O1CCCC1.C(OCC)(=O)C>[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]=[CH:32][C:33]([F:36])=[C:34]([F:35])[C:29]=1[F:28])(=[O:39])=[O:38]

Participants

6

Reactant 3

HCID 2733832Lithium Hexamethyldisilazide2×HCID 27769772,3,4-Trifluorobenzenesulfonyl chloride2×HCID 57732216N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine

Product 1

HCID 89545477HCID 89545477, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (3.0 g, 12 mmol) in tetrahydrofuran (50 mL) at −78° C. was added lithium bis(trimethylsilyl)amide (1 M solution in tetrahydrofuran, 15.5 mL, 15.5 mmol). The reaction mixture was allowed to warm to ambient temperature. After 1 h, the reaction mixture was cooled to −78° C. and 2,3,4-trifluorobenzene-1-sulfonyl chloride (1.8 mL, 12 mmol) was added. After 2 further lithium bis(trimethylsilyl)amide (1 M solution in tetrahydrofuran, 2.4 mL, 2.4 mmol) and 2,3,4-trifluorobenzene-1-sulfonyl chloride (0.3 mL, 2.4 mmol) were added. After 1 h, the reaction mixture was allowed to warm to ambient temperature, diluted with ethyl acetate (150 mL), washed with saturated ammonium chloride (2×125 mL) and brine (2×125 mL), dried over sodium sulfate and concentrated in vacuo. The residue was triturated with methanol to afford N-(2,4-dimethoxybenzyl)-2,3,4-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a pale yellow solid in 67% yield (3.5 g).

Workup

  1. temperaturethe reaction mixture was cooled to −78° C.
  2. waitAfter 1 h
  3. temperatureto warm to ambient temperature
  4. washwashed with saturated ammonium chloride (2×125 mL) and brine (2×125 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was triturated with methanol

Sources & evidence

ORD record
ord-4bab82bd77c045b0afa53570d6024573
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

Loading…