Tetrahydrofuran → (4-{1-Ethyl-1-[4-(2-hydroxy-3,3-dimethyl-butoxy)-3-methyl-phenyl]-propyl}-2-methyl-benzyloxy)-acetic acid

HRID 230820Notes

Reaction equation

HRID 230820 reaction equation
C[O:2][C:3](=[O:41])[CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]([O:31][Si](C(C)(C)C)(C)C)[C:27]([CH3:30])([CH3:29])[CH3:28])=[C:20]([CH3:39])[CH:19]=2)([CH2:16][CH3:17])[CH2:14][CH3:15])=[CH:9][C:8]=1[CH3:40].C1COCC1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].[OH-].[Na+]>O>[CH2:14]([C:13]([C:10]1[CH:11]=[CH:12][C:7]([CH2:6][O:5][CH2:4][C:3]([OH:41])=[O:2])=[C:8]([CH3:40])[CH:9]=1)([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]([OH:31])[C:27]([CH3:29])([CH3:30])[CH3:28])=[C:20]([CH3:39])[CH:19]=1)[CH2:16][CH3:17])[CH3:15]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 2724141Tetrabutylammonium FluorideHCID 57763463[4-(1-{4-[2-(tert-Butyl-dimethyl-silanyloxy)-3,3-dimethyl-butoxy]-3-methyl-phenyl}-1-ethyl-propyl)-2-methyl-benzyloxy]-acetic acid methyl ester

Product 1

HCID 57763426(4-{1-Ethyl-1-[4-(2-hydroxy-3,3-dimethyl-butoxy)-3-methyl-phenyl]-propyl}-2-methyl-benzyloxy)-acetic acidYield 60.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of enantiomer 1 of [4-(1-{4-[2-(tert-butyl-dimethyl-silanyloxy)-3,3-dimethyl-butoxy]-3-methyl-phenyl}-1-ethyl-propyl)-2-methyl-benzyloxy]-acetic acid methyl ester (0.96 g, 1.64 mmol) and THF (10 mL) is added 1M TBAF (3.3 mL, 3.28 mmol). The solution is heated at a reflux overnight and concentrated. The residue is dissolved in MeOH (5 mL) and water (1 mL), NaOH (0.33 g, 8.21 mmol) is added and the solution is heated at reflux for 3 hours. The solution is concentration, dissolved in EtOAc (20 mL), washed with 1M HCl (15 mL), water (15 mL), brine (15 mL), dried over MgSO4, and concentrated. The residue is chromatographed to furnish the title compound (0.45 g, 0.99 mmol, 60%).

Workup

  1. temperatureThe solution is heated at a reflux overnight
  2. concentrationconcentrated
  3. dissolutionThe residue is dissolved in MeOH (5 mL)
  4. temperaturethe solution is heated
  5. temperatureat reflux for 3 hours
  6. concentrationconcentration
  7. dissolutiondissolved in EtOAc (20 mL)
  8. washwashed with 1M HCl (15 mL), water (15 mL), brine (15 mL)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe residue is chromatographed

Sources & evidence

ORD record
ord-fb226fd1141240c083418946d8e04b64
Source dataset
uspto-grants-2009_07
Patent number
US07566803B2

Reaction notes

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