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

HRID 2203464Notes

Reaction equation

HRID 2203464 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]([N-][Si](C)(C)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.C(OCC)(=O)C>[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

6

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 62%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of tert-butyl thiazol-4-ylcarbamate (3.46 g, 17.3 mmol) in tetrahydrofuran (150 mL) at −78° C. was treated with lithium bis(trimethylsilyl)amide (1.0 M solution in tetrahydrofuran, 20.8 mL, 20.8 mmol). The resulting mixture was stirred at −78° C. for 0.5 h, allowed to warm to ambient temperature and stirred for a further 0.5 h. The reaction mixture was cooled to −78° C. and treated with a solution of 2,4,5-trifluorobenzene-1-sulfonyl chloride (3.99 g, 17.3 mmol) in tetrahydrofuran (30 mL). The resulting mixture was stirred at −78° C. for 4 h, allowed to warm to ambient temperature and stirred for a further 16 h. The reaction mixture was diluted with ethyl acetate (300 mL) and washed with saturated aqueous ammonium chloride (2×150 mL) and brine (2×150 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a gradient of ethyl acetate in hexanes to afford tert-butyl thiazol-4-yl((2,4,5-trifluorophenyl)sulfonyl)carbamate as a beige solid in 62% yield (4.23 g): 1H NMR (300 MHz, CDCl3) δ 8.79-8.75 (m, 1H), 8.06-7.96 (m, 1H), 7.53-7.48 (m, 1H), 7.15-7.04 (m, 1H), 1.34 (s, 9H); MS (ES+) m/z 394.7 (M+1).

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for a further 0.5 h
  3. temperatureThe reaction mixture was cooled to −78° C.
  4. stirringThe resulting mixture was stirred at −78° C. for 4 h
  5. temperatureto warm to ambient temperature
  6. stirringstirred for a further 16 h
  7. washwashed with saturated aqueous ammonium chloride (2×150 mL) and brine (2×150 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography
  12. washeluting with a gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-a849ea9d65bb4c3fb3720609c619b0d6
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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