Ammonium Chloride → tert-Butyl [(3-cyano-4-fluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamate

HRID 46319

Reaktionsgleichung

Reaktionsgleichung von HRID 46319
[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](C)(C)[N-][Si](C)(C)C.[Li+].[C:24]([C:26]1[CH:27]=[C:28]([S:33](Cl)(=[O:35])=[O:34])[CH:29]=[CH:30][C:31]=1[F:32])#[N:25].[Cl-].[NH4+]>O1CCCC1>[C:24]([C:26]1[CH:27]=[C:28]([S:33]([N:6]([C:4]2[N:3]=[CH:2][S:1][CH:5]=2)[C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])(=[O:35])=[O:34])[CH:29]=[CH:30][C:31]=1[F:32])#[N:25]

Komponenten

6

Edukt 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27789083-Cyano-4-fluorobenzenesulfonyl chlorideHCID 53241636tert-butyl N-(1,3-thiazol-4-yl)carbamate

Produkt 1

HCID 59436569tert-Butyl [(3-cyano-4-fluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamateAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a stirred solution of tert-butyl 1,3-thiazol-4-ylcarbamate (Preparation 72, 0.500 g, 0.002497 mol) in tetrahydrofuran (10.0 mL) was added lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1.0 M solution in tetrahydrofuran, 2.50 mL, 0.0025 mol) at 0° C. under nitrogen. After stirring for 1 hour at 0° C. the reaction mixture was cooled to −78° C. and 3-cyano-4-fluorobenzenesulfonyl chloride (0.453 g, 0.002063 mol) in tetrahydrofuran (5.0 mL) was added. The mixture was warmed to room temperature for 16 hours. Saturated aqueous ammonium chloride solution (20.0 mL) was added and the aqueous layer was extracted with ethyl acetate (3×20.0 mL). Combined organic layers were dried over sodium sulfate and concentrated in vacuo. This crude residue was purified using ISCO™ (12 g SiO2) eluting with ethyl acetate:dichloromethane (gradient 0:1 to 3:7, by volume) to afford the title compound as a white solid, 426 mg, 54% yield.

Aufarbeitung

  1. temperaturewas cooled to −78° C.
  2. temperatureThe mixture was warmed to room temperature for 16 hours
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×20.0 mL)
  4. dry with materialCombined organic layers were dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThis crude residue was purified
  7. washeluting with ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-458284f2350a4290a63c9c1551ccfac1
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541588B2

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