Carbon Dioxide → Tert-butyl (5-chloro-2,4-difluorophenyl)sulfonyl(thiazol-4-yl)carbamate

HRID 46343

Reaction equation

HRID 46343 reaction equation
[C:1]([O:5][C:6](=[O:13])[NH:7][C:8]1[N:9]=[CH:10][S:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[Cl:24][C:25]1[C:26]([F:36])=[CH:27][C:28]([F:35])=[C:29]([S:31](Cl)(=[O:33])=[O:32])[CH:30]=1.C(=O)=O.[Cl-].[NH4+]>O1CCCC1>[Cl:24][C:25]1[C:26]([F:36])=[CH:27][C:28]([F:35])=[C:29]([S:31]([N:7]([C:8]2[N:9]=[CH:10][S:11][CH:12]=2)[C:6](=[O:13])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])(=[O:33])=[O:32])[CH:30]=1

Participants

7

Reactant 5

HCID 280Carbon DioxideHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27735275-Chloro-2,4-difluorobenzenesulphonyl chlorideHCID 53241636tert-butyl N-(1,3-thiazol-4-yl)carbamate

Product 1

HCID 59436581Tert-butyl (5-chloro-2,4-difluorophenyl)sulfonyl(thiazol-4-yl)carbamateYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of thiazol-4-yl-carbamic acid tert-butyl ester (Preparation 72, 503 mg, 0.00251 mol) in tetrahydrofuran (5.0 mL) cooled to −78° C. was added lithium hexamethyldisilazide (1.0 M in tetrahydrofuran, 2.76 mL, 0.00276 mol). The reaction was stirred for 30 minutes at room temperature and then cooled to −78° C. A solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride (620.5 mg, 0.002512 mol) in tetrahydrofuran (5.0 mL) was added slowly via syringe. After addition was complete, the reaction mixture remained immersed in the cooling bath; the temperature of the dry ice bath was not maintained, allowing the reaction mixture to slowly warm to room temperature. After 24 hours, the reaction mixture was poured into saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered and concentrated in vacuo onto Celite™. The residue was purified by automated flash chromatography (40 g SiO2) eluting with ethyl acetate:dichloromethane (gradient 0:1 to 5:95, by volume) to afford the title compound as a white solid, 733 mg, 71% yield.

Workup

  1. temperaturecooled to −78° C
  2. additionAfter addition
  3. temperatureto slowly warm to room temperature
  4. waitAfter 24 hours
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo onto Celite™
  9. customThe residue was purified by automated flash chromatography (40 g SiO2)
  10. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-55887764a0214dc293f0f70acde56115
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Linked notes

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