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

HRID 2283623Notes

Reaction equation

HRID 2283623 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.[Cl-].[NH4+]>O1CCCC1>[C:1]([O:5][C:6](=[O:13])[N:7]([S:31]([C:29]1[CH:30]=[C:25]([Cl:24])[C:26]([F:36])=[CH:27][C:28]=1[F:35])(=[O:33])=[O:32])[C:8]1[N:9]=[CH:10][S:11][CH:12]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 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 71.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of thiazol-4-yl-carbamic acid tert-butyl ester (Preparation 3, 503 mg, 2.51 mmol) in tetrahydrofuran (5.0 mL) cooled to −78° C. was added lithium hexamethyldisilazide (1.0 M in tetrahydrofuran, 2.76 mL, 2.76 mmol). The reaction mixture was stirred for 30 minutes at ambient temperature then cooled to −78° C. A solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride (620.5 mg, 2.51 mmol) in tetrahydrofuran (5.0 mL) was added slowly via a syringe. After the addition was complete, the reaction mixture was allowed to warm gradually to ambient 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 anhydrous magnesium sulfate, filtered and concentrated in vacuo onto diatomaceous earth. The residue was purified by automated silica gel flash chromatography (0% to 5% ethyl acetate in dichloromethane gradient elution) to afford the title compound as a white solid (733 mg).

Workup

  1. temperaturethen cooled to −78° C
  2. additionAfter the addition
  3. temperatureto warm gradually to ambient temperature
  4. waitAfter 24 hours
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo onto diatomaceous earth
  9. customThe residue was purified by automated silica gel flash chromatography (0% to 5% ethyl acetate in dichloromethane gradient elution)

Sources & evidence

ORD record
ord-134cf5c09d334274b921fecda72296c3
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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