4-Bromo-2-fluorotoluene → 4,5-Dihydro-5,5-dimethyl-2-(3'-fluoro-4'-methyl-biphenyl-2-yl)oxazole

HRID 343955

Reaction equation

HRID 343955 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[C:5]([F:10])[CH:4]=1.[CH3:11][C:12]1([CH3:25])[O:16][C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2OC)=[N:14][CH2:13]1>O1CCCC1>[CH3:11][C:12]1([CH3:25])[O:16][C:15]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=2[C:3]2[CH:8]=[CH:7][C:6]([CH3:9])=[C:5]([F:10])[CH:4]=2)=[N:14][CH2:13]1

Participants

5

Reactant 3

HCID 1710404-Bromo-2-fluorotolueneHCID 5462224MagnesiumHCID 542759394,5-Dihydro-5,5-dimethyl-2-(2-methoxyphenyl)-oxazole

Product 1

HCID 545155994,5-Dihydro-5,5-dimethyl-2-(3'-fluoro-4'-methyl-biphenyl-2-yl)oxazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

14.7 g (605.7 mol) of magnesium filings are initially introduced into 50 ml of analytical grade tetrahydrofuran under argon, and 117.7 g (623 mmol) of 4-bromo-2-fluoro-toluene in 500 ml of analytical grade tetrahydrofuran are added, while stirring. A clear solution forms at 35°-40° C. within 2 hours. A solution of 74.0 g (360.5 mmol) of the compound from Example II in 500 ml of analytical grade tetrahydrofuran is added dropwise at room temperature and the mixture is subsequently stirred at about 25° C. for 16 hours, initially with gentle cooling. The solvent is evaporated off and the crude product is subsequently rinsed in 600 ml of ethyl acetate and 800 ml of saturated ammonium chloride solution at 10° C., dried with sodium sulphate and evaporated in vacuo. For purification, the product is taken up in 600 ml of ether, any solid residue is filtered off with suction and the crude product is extracted into the aqueous phase by several extractions with 2M hydrochloric acid. This aqueous phase is covered with a layer of ether and brought to pH 13 with sodium hydroxide solution. After three extractions with ether, the product phase is dried with sodium sulphate and evaporated and the residual solvent is removed under a high vacuum.

Workup

  1. stirringthe mixture is subsequently stirred at about 25° C. for 16 hours, initially with gentle cooling
  2. customThe solvent is evaporated off
  3. washthe crude product is subsequently rinsed in 600 ml of ethyl acetate
  4. dry with material800 ml of saturated ammonium chloride solution at 10° C., dried with sodium sulphate
  5. customevaporated in vacuo
  6. customFor purification
  7. filtrationany solid residue is filtered off with suction
  8. extractionthe crude product is extracted into the aqueous phase by several extractions with 2M hydrochloric acid
  9. extractionAfter three extractions with ether
  10. dry with materialthe product phase is dried with sodium sulphate
  11. customevaporated
  12. customthe residual solvent is removed under a high vacuum

Sources & evidence

ORD record
ord-beb80e27ccf5471aa0e578be941d7c9a
Source dataset
uspto-grants-1999_01
Patent number
US05863930

Linked notes

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