Sodium Hydroxide → HCID 57707243, compound

HRID 1662437Notes

Reaction equation

HRID 1662437 reaction equation
[CH:1]1([O:4][C:5]2[CH:6]=[C:7]([C:11]3[CH:16]=[CH:15][C:14]([C:17](OC)=[O:18])=[CH:13][C:12]=3[CH:21]3[CH2:25][CH2:24][CH2:23][C:22]3([CH3:27])[CH3:26])[CH:8]=[CH:9][CH:10]=2)[CH2:3][CH2:2]1.[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+]>C1COCC1>[CH:1]1([O:4][C:5]2[CH:6]=[C:7]([C:11]3[CH:16]=[CH:15][C:14]([CH2:17][OH:18])=[CH:13][C:12]=3[CH:21]3[CH2:25][CH2:24][CH2:23][C:22]3([CH3:27])[CH3:26])[CH:8]=[CH:9][CH:10]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 57706973HCID 57706973, compound

Product 1

HCID 57707243HCID 57707243, compoundYield 83.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled solution of 66.48C (0.4115 g, 1.129 mmol) in dry THF (10 mL) at 0° C. was added LAH (1.0M in THF) (2.30 mL, 2.3 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. The resulting mixture 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 a colorless oil as 66.48D (317.1 mg, 83% yield). MS ESI (pos.) m/e: 319.0 (M−H2O)+. Chiral separation of 66.48D was accomplished on Chiracel-OD (3% IPA in hexane) to provide 66.48E (peak 1) and 66.48F (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 mixture 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

Sources & evidence

ORD record
ord-fccc894c05294967a8829cb4e4250a33
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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