Water → HCID 58047205, compound

HRID 1888759Notes

Reaction equation

HRID 1888759 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][C:14]3[CH:23]=[CH:22][C:17]([C:18](OC)=[O:19])=[C:16]([O:24][CH2:25][O:26][CH3:27])[CH:15]=3)=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]([CH2:12][CH2:13][C:14]3[CH:23]=[CH:22][C:17]([CH2:18][OH:19])=[C:16]([O:24][CH2:25][O:26][CH3:27])[CH:15]=3)=[CH:10][CH:11]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 67015762HCID 67015762, compound

Product 1

HCID 58047205HCID 58047205, compoundYield 97.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of methyl 2-(methoxymethoxy)-4-[(4-benzyloxyphenyl)ethynyl]benzoate (7.37 g, 18.3 mmol) obtained in Reference Example 277 and 10% palladium carbon (50% water-containing product, 11.0 g) in ethanol (50 mL)-THF (10 mL) was stirred under a hydrogen atmosphere (normal pressure) for 2 hr. After filtration of the reaction mixture, the filtrate was concentrated under reduced pressure. To a solution of the obtained residue in DMF (50 mL) were added potassium carbonate (7.63 g, 55.2 mmol) and bromomethylcyclopropane (3.60 mL, 36.7 mmol) and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was washed three times with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by basic silica gel column chromatography (hexane:ethyl acetate=9:1 to 1:1) to give methyl 4-{2-[4-(cyclopropylmethoxy)phenyl]ethyl}-2-(methoxymethoxy)benzoate (4.69 g, yield 69%). A solution of methyl 4-{2-[4-(cyclopropylmethoxy)phenyl]ethyl}-2-(methoxymethoxy)benzoate (4.69 g, 12.7 mmol) in THF (10 mL) was added to a suspension of lithium aluminum hydride (481 mg, 12.7 mmol) in THF (30 mL), and the mixture was stirred at room temperature for 15 min. To the reaction mixture were successively added water (0.48 mL), 15% aqueous sodium hydroxide solution (0.48 mL) and water (1.5 mL), and the mixture was stirred at room temperature for 30 min. After filtration, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=7:3 to 0:1) to give the title compound (4.23 g, yield 97%) as an oil.

Workup

  1. stirringthe mixture was stirred at room temperature for 30 min
  2. filtrationAfter filtration
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customthe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=7:3 to 0:1)

Sources & evidence

ORD record
ord-89a40a25e63346288173a3c7c7e495c3
Source dataset
uspto-grants-2013_08
Patent number
US08501804B2

Reaction notes

Loading…