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

HRID 858262

Reaction equation

HRID 858262 reaction equation
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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 31347SulfolaneSolvent

Procedure

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/e 290 (M+H)+.

Workup

  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%)

Sources & evidence

ORD record
ord-4b294c5a3f1048988ecb57ea27498e45
Source dataset
uspto-grants-2006_12
Patent number
US07148247B2

Linked notes

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