Sodium Hydroxide → (5'-(Difluoromethyl)-2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-1,1'-biphenyl-4-yl)methanol

HRID 404373Notes

Reaction equation

HRID 404373 reaction equation
[F:1][CH:2]([F:27])[C:3]1[CH:4]=[CH:5][C:6]([F:26])=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([C:15](OC)=[O:16])=[CH:11][C:10]=2[C:19]2[C:23]([CH3:25])([CH3:24])[CH2:22][CH2:21][CH:20]=2)[CH:8]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+]>C1COCC1>[F:27][CH:2]([F:1])[C:3]1[CH:4]=[CH:5][C:6]([F:26])=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][OH:16])=[CH:11][C:10]=2[C:19]2[C:23]([CH3:24])([CH3:25])[CH2:22][CH2:21][CH:20]=2)[CH:8]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 57705519Methyl 5'-(difluoromethyl)-2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-1,1'-biphenyl-4-carboxylate

Product 1

HCID 57706435(5'-(Difluoromethyl)-2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-1,1'-biphenyl-4-yl)methanolYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled solution of T34.2 (0.2349 g, 0.6274 mmol) in dry THF (5 mL) at 0° C. was added LAH (1.0 M in THF)(1.3 mL, 1.3 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 a colorless oil as T34.3 (166.6 mg, 77% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.47 (2H, m), 7.38 (2H, m), 7.14 (1H, t, J=9.0 Hz), 6.62 (1H, t), 5.50 (1H, td, J=2.4, 1.0 Hz), 4.76 (2H, s), 2.23 (2H, td, J=7.0, 2.3 Hz), 1.74 (3H, 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 to a colorless oil as T34.3 (166.6 mg, 77% yield)

Sources & evidence

ORD record
ord-3867c91b02c4450b9a72c45ed747a1f9
Source dataset
uspto-grants-2014_06
Patent number
US08748462B2

Reaction notes

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