1,3-Dibromo-5,5-dimethylhydantoin → 7-(2-Bromo-1-fluoroethyl)-2-(3-fluoro-4-hydroxyphenyl)-1,3-benzoxazol-5-ol

HRID 491760

Reaktionsgleichung

Reaktionsgleichung von HRID 491760
N1C=CC=CC=1.[FH:7].C([O:11][C:12]1[CH:13]=[C:14]([CH:32]=[CH2:33])[C:15]2[O:19][C:18]([C:20]3[CH:25]=[CH:24][C:23]([O:26]C(=O)C)=[C:22]([F:30])[CH:21]=3)=[N:17][C:16]=2[CH:31]=1)(=O)C.[Br:34]N1C(C)(C)C(=O)N(Br)C1=O>S1(CCCC1)(=O)=O.Cl>[Br:34][CH2:33][CH:32]([C:14]1[C:15]2[O:19][C:18]([C:20]3[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([F:30])[CH:21]=3)=[N:17][C:16]=2[CH:31]=[C:12]([OH:11])[CH:13]=1)[F:7]

Komponenten

6

Edukt 3

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 64774Pyridine, hydrofluoride (1:1)HCID 112682632-[4-(Acetyloxy)-3-fluorophenyl]-7-vinyl-1,3-benzoxazol-5-yl acetate

Produkt 1

HCID 1363776577-(2-Bromo-1-fluoroethyl)-2-(3-fluoro-4-hydroxyphenyl)-1,3-benzoxazol-5-ol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 31347SulfolaneLösungsmittel

Versuchsvorschrift

Hydrogen fluoride pyridine (1.14 mL) was added dropwise into a cold (0° C.) solution of 2-[4-(acetyloxy)-3-fluorophenyl]-7-vinyl-1,3-benzoxazol-5-yl acetate (0.25 g, 0.7 mmol), in sulfolane (3 mL). The reaction mixture was stirred for 5 min and then 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione (120 mg) was added in one portion. The mixture was stirred at room temperature for 24 h, diluted with HCl (1N) and extracted with EtOAc. The organic layer was dried over MgSO4. Evaporation and purification by flash chromatography (CH2Cl2/isopropyl alcohol 0.3%) gave 7-(2-bromo-1-fluoroethyl)-2-(3-fluoro-4-hydroxyphenyl)-1,3-benzoxazol-5-ol as a white solid (0.25 g, m.p. 185-186° C.). The product was taken in acetonitrile (2 mL) and 1,8-diazabicyclo[5.4.0]undec-7-ene (150 mg) was added. The reaction mixture was stirred for 24 h, poured into cold (0° C.) HCl (1N, 10 mL) and extracted with EtOAc. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography (20% EtOAc/hexanes) gave a white solid (160 mg, m.p. 213-214° C.); MS m/e290 (M+H)+.

Aufarbeitung

  1. stirringThe mixture was stirred at room temperature for 24 h
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over MgSO4
  4. customEvaporation and purification by flash chromatography (CH2Cl2/isopropyl alcohol 0.3%)

Quellen und Nachweise

ORD-Eintrag
ord-5114997fc39f4f7c836feb93add59373
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07531564B2

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