Tetrahydrofuran → 5-fluoro-3-[1-hydroxy-1-(thiazol-2-yl)propyl](O-benzyl)phenol

HRID 741794Notes

Reaction equation

HRID 741794 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11](Br)[CH:12]=[C:13]([F:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Mg].[S:18]1[CH:22]=[CH:21][N:20]=[C:19]1[CH2:23][C:24](=O)[CH3:25].C1C[O:30]CC1>>[F:15][C:13]1[CH:12]=[C:11]([C:23]([OH:30])([C:19]2[S:18][CH:22]=[CH:21][N:20]=2)[CH2:24][CH3:25])[CH:10]=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:14]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 5462224MagnesiumHCID 112545161-(Benzyloxy)-3-bromo-5-fluorobenzeneHCID 231799141-(Thiazol-2-yl)propanone

Product 1

HCID 199096325-fluoro-3-[1-hydroxy-1-(thiazol-2-yl)propyl](O-benzyl)phenolYield 50%

Procedure

A solution of 3-benzyloxy-1-bromo-5-fluorobenzene (EP: 0385662, ICI, Pharma) (5.4 g, 19.4 mmol) in dry THF (30 mL) containing magnesium (941 mg, 38.7 mmol) was heated until the Grignard reagent was formed then the reaction mixture was stirred at r.t. for 30 min. and transferred to a solution of 1-(thiazol-2-yl)propanone in dry THF at 0° C. The reaction mixture was stirred for 30 min. then an aqueous solution of NH4OAc (25%) was added and the THF evaporated. The residue was diluted with EtOAc and washed successively with H2O, brine, dried over MgSO4 and evaporated. The residue was purified by chromatography using hexane:EtOAc 9:1 to give 2.2 g, (50%) of the title product.

Workup

  1. customwas formed
  2. stirringThe reaction mixture was stirred for 30 min.
  3. customthe THF evaporated
  4. additionThe residue was diluted with EtOAc
  5. washwashed successively with H2O, brine
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-7e48b88b910645ac9d51e4914b3797d4
Source dataset
uspto-grants-1996_09
Patent number
US05552437

Reaction notes

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