Tetrahydrofuran → (2-(1,1-Dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methanol

HRID 1662328Notes

Reaction equation

HRID 1662328 reaction equation
[CH3:1][C:2]([C:5]1[CH:10]=[C:9]([C:11](OC)=[O:12])[CH:8]=[CH:7][C:6]=1[C:15]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:16]=1[F:23])([CH3:4])[CH3:3].C1COCC1.[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+]>>[CH3:4][C:2]([C:5]1[CH:10]=[C:9]([CH2:11][OH:12])[CH:8]=[CH:7][C:6]=1[C:15]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:16]=1[F:23])([CH3:1])[CH3:3]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 57705886Methyl 2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

Product 1

HCID 57705540(2-(1,1-Dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methanolYield 72.2%

Procedure

To a cooled solution of 8.8 (0.85 g, 2.69 mmol) in dry THF (10.0 mL, 2.69 mmol) at 0° C., was added LAH (1.0 M solution in THF (6.0 mL, 6.0 mmol)). Upon complete addition, the reaction was allowed to warm to room temperature and monitored by TLC and LCMS. Upon completion, 1N NaOH (5 mL) was carefully added to quench the reaction. The resulting solution was extracted with EtOAc (3×10 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%-40% EtOAc in hexanes). Fractions containing the desired product were combined and concentrated to provide 8.9 as a colorless oil (0.56 g, 72%). MS ESI (pos.) m/e: 311.2 (M+Na)+.

Workup

  1. additionUpon complete addition
  2. customto quench
  3. customthe reaction
  4. extractionThe resulting solution was extracted with EtOAc (3×10 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was then purified by flash chromatography (SiO2 gel 60, eluted with 0%-40% EtOAc in hexanes)
  9. additionFractions containing the desired product
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-48ca87bcf71a4d9fa8c8ab982ed0fd55
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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