Sodium Hydroxide → (2-(5,5-Dimethyl-1-cyclopenten-1-yl)-2',5-difluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methanol

HRID 1662524Notes

Reaction equation

HRID 1662524 reaction equation
[CH3:1][C:2]1([CH3:27])[C:6]([C:7]2[CH:12]=[C:11]([C:13](OC)=[O:14])[C:10]([F:17])=[CH:9][C:8]=2[C:18]2[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=2[F:26])=[CH:5][CH2:4][CH2:3]1.[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+]>C1COCC1>[CH3:1][C:2]1([CH3:27])[C:6]([C:7]2[CH:12]=[C:11]([CH2:13][OH:14])[C:10]([F:17])=[CH:9][C:8]=2[C:18]2[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=2[F:26])=[CH:5][CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 57706663Methyl 2-(5,5-dimethyl-1-cyclopenten-1-yl)-2',5-difluoro-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

Product 1

HCID 57705862(2-(5,5-Dimethyl-1-cyclopenten-1-yl)-2',5-difluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a cooled solution of 83.2G (0.92 g, 2.47 mmol) in dry THF (15 mL) at 0° C. was added LAH, 1.0 M in THF (5.0 mL, 5.0 mmol) dropwise. Upon complete addition, the reaction was maintained at 0° C. and was monitored by TLC and LCMS. After 45 minutes, 1N NaOH was added to quench the reaction (gas evolution occurred). The resulting solution was extracted three times with EtOAc. After drying over anhydrous magnesium sulfate, filtration, and concentration, the residue was then purified by flash chromatography (SiO2 gel 60, eluted with 0%-50% EtOAc in hexanes). Fractions containing the desired product were combined and concentrated to provide 83.2H as a colorless oil (0.70 g, 82%). 1H NMR (500 MHz, CDCl3) δ ppm 7.30 (1H, m), 7.05 (1H, dd, J=10.6, 1.1 Hz), 6.97 (1H, t, J=8.9 Hz), 6.83 (2H, m), 5.52 (1H, td, J=2.4, 0.9 Hz), 4.81 (2H, s), 3.76 (3H, s), 2.25 (2H, td, J=7.1, 2.4 Hz), 1.76 (1H, br. s.), 1.69 (2H, m), 0.85 (6H, s).

Workup

  1. additionUpon complete addition
  2. customto quench
  3. customthe reaction (gas evolution occurred)
  4. extractionThe resulting solution was extracted three times with EtOAc
  5. dry with materialAfter drying over anhydrous magnesium sulfate, filtration, and concentration
  6. customthe residue was then purified by flash chromatography (SiO2 gel 60, eluted with 0%-50% EtOAc in hexanes)
  7. additionFractions containing the desired product
  8. concentrationconcentrated
  9. customto provide 83.2H as a colorless oil (0.70 g, 82%)

Sources & evidence

ORD record
ord-1a9b3491b6bd41679fa6733465ce50e9
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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