Tetrahydrofuran → 2-(Isochroman-1-yl)-2-methylpropionic acid

HRID 368830Notes

Reaction equation

HRID 368830 reaction equation
[OH-].[Na+].C1COCC1.[CH:8]1([C:18]([CH3:24])([CH3:23])[C:19]([O:21]C)=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10][O:9]1>C(O)C>[CH:8]1([C:18]([CH3:24])([CH3:23])[C:19]([OH:21])=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10][O:9]1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 14798Sodium Hydroxide2×HCID 23288833Methyl 2-(isochroman-1-yl)-2-methylpropionate

Product 1

HCID 232888942-(Isochroman-1-yl)-2-methylpropionic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium hydroxide (1N, 12 ml) is added dropwise over several minutes, followed by a few mls of THF (to aid in solution) to a mixture of methyl 2-(isochroman-1-yl)-2-methylpropionate (LXXI, 1.833 g, 7.8 mmol) in ethanol (12 ml). The mixture is stirred overnight at 20-25°, then at 47° for 2 hr, followed by stirring at 20-25° over the weekend. Additional THF and sodium hydroxide (1N, 12 ml) are added and the mixture is stirred overnight at 20-25° and then at 40° for 7 hr, followed by overnight at 20-25°. Ethanol is then removed under reduced pressure and the resulting solids are dissolved in water. The aqueous phase is separated and washed twice with hexane to remove any unreacted starting material and the aqueous phase is then cooled in an ice/water bath and hydrochloric acid (4N, 6 ml) is added dropwise. The mixture is extracted three times with ether and the combined organic phases are backwashed with saline, dried over magnesium sulfate, and concentrated. Recrystallization from dichloromethanemexane gives 2-(isochroman-1-yl)-2-methylpropionic acid (LXXII), mp 110.5-115.75°.

Workup

  1. waitat 47° for 2 hr
  2. stirringby stirring at 20-25° over the weekend
  3. stirringthe mixture is stirred overnight at 20-25°
  4. waitat 40° for 7 hr
  5. waitfollowed by overnight at 20-25°
  6. customEthanol is then removed under reduced pressure
  7. dissolutionthe resulting solids are dissolved in water
  8. customThe aqueous phase is separated
  9. washwashed twice with hexane
  10. customto remove
  11. temperaturethe aqueous phase is then cooled in an ice/water bath
  12. additionhydrochloric acid (4N, 6 ml) is added dropwise
  13. extractionThe mixture is extracted three times with ether
  14. dry with materialdried over magnesium sulfate
  15. concentrationconcentrated
  16. customRecrystallization from dichloromethanemexane

Sources & evidence

ORD record
ord-6def33753c594eb9a3217cf485d70631
Source dataset
uspto-grants-2000_10
Patent number
US06133446

Reaction notes

Loading…