Boron tribromide → Methyl 2-(1,1-dimethylethyl)-2'-fluoro-5'-hydroxy-1,1'-biphenyl-4-carboxylate

HRID 1662343Notes

Reaction equation

HRID 1662343 reaction equation
[CH3:1][C:2]([C:5]1[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[CH:7][C:6]=1[C:15]1[CH:20]=[C:19]([O:21]C)[CH:18]=[CH:17][C:16]=1[F:23])([CH3:4])[CH3:3].B(Br)(Br)Br>C(Cl)Cl>[CH3:4][C:2]([C:5]1[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[CH:7][C:6]=1[C:15]1[CH:20]=[C:19]([OH:21])[CH:18]=[CH:17][C:16]=1[F:23])([CH3:1])[CH3:3]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 57705886Methyl 2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

Product 1

HCID 57706306Methyl 2-(1,1-dimethylethyl)-2'-fluoro-5'-hydroxy-1,1'-biphenyl-4-carboxylateYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled solution of 8.8 (0.500 g, 2.00 mmol) in dry DCM (32.0 mL) at 0° C. was added boron tribromide (7.00 mL, 7.00 mmol). Stirring was continued for 6 hours, and the reaction was monitored by TLC and LCMS. Upon completion, pH 7 buffer was added to the mixture at 0° C. The resulting solution was extracted with DCM (3×20 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was then purified by flash chromatography (SiO2 gel 60, eluted with 0%-20% EtOAc in hexanes). Fractions containing the desired product were combined and concentrated to provide 35.1 as a colorless oil (0.29 g, 61%). MS ESI (pos.) m/e: 335.1 (M+Na)+, 320.1 (M+H2O)+, 303.1 (M+H)+.

Workup

  1. additionUpon completion, pH 7 buffer was added to the mixture at 0° C
  2. extractionThe resulting solution was extracted with DCM (3×20 mL)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was then purified by flash chromatography (SiO2 gel 60, eluted with 0%-20% EtOAc in hexanes)
  7. additionFractions containing the desired product
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-aa582671fd2140e28b0c6ed7ebfea3ad
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

Loading…