Sodium Hydroxide → HCID 57705887, compound

HRID 1662535Notes

Reaction equation

HRID 1662535 reaction equation
[CH3:1][C:2]1([CH3:27])[CH2:6][CH2:5][CH2:4][CH:3]1[C:7]1[CH:12]=[C:11]([C:13](OC)=[O:14])[CH:10]=[C:9]([F:17])[C:8]=1[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=1[F:26].[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+]>C1COCC1>[CH3:1][C:2]1([CH3:27])[CH2:6][CH2:5][CH2:4][CH:3]1[C:7]1[CH:12]=[C:11]([CH2:13][OH:14])[CH:10]=[C:9]([F:17])[C:8]=1[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=1[F:26]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 57706393HCID 57706393, compound

Product 1

HCID 57705887HCID 57705887, compoundYield 46.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled solution of 83.20A (0.7036 g, 1.879 mmol) in dry THF (15 mL) at 0° C. was added LAH (1.0 M in THF) (4 mL, 4.0 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 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 a colorless oil that solidified as 83.20B (300.5 mg, 46% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.16 (1H, s), 7.10 (2H, m), 6.92 (1H, m), 6.77 (1H, dd, J=5.9, 3.1 Hz), 4.74 (2H, s), 3.81 (3H, m), 2.73 (1H, ddd, J=10.3, 8.3, 1.8 Hz), 2.17 (1H, m), 2.04 (1H, m), 1.87 (1H, m), 1.73 (3H, m), 1.42 (1H, m), 0.78 (3H, s), 0.64 (3H, s). Chiral separation of 83.20B was accomplished on Chiracel-OJ (2% IPA in hexane) to provide 83.20C (peak 1) and 83.20D (peak 2). Both enantiomers were used to synthesize example compounds, and both enantiomers gave active compounds.

Workup

  1. additionUpon complete addition
  2. customto quench
  3. customthe reaction
  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 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 a colorless oil that

Sources & evidence

ORD record
ord-2ebd4c0bd1c1451f84a5eec6db1a7e46
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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