Diisopropylamine → (+/-)-2-(1-Naphthoxy)-6-phenylhexanoic acid

HRID 1607404Notes

Reaction equation

HRID 1607404 reaction equation
[H-].[Na+].C(NC(C)C)(C)C.[C:10]1([O:20][CH2:21][C:22]([OH:24])=[O:23])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1.C([Li])CCC.CCCCCC.[C:36]1([CH2:42][CH2:43][CH2:44][CH2:45]Br)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>O1CCCC1>[C:10]1([O:20][CH:21]([CH2:45][CH2:44][CH2:43][CH2:42][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:22]([OH:24])=[O:23])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1

Participants

8

Reactant 6

HCID 7912DiisopropylamineHCID 8058HexaneHCID 24758Sodium hydrideHCID 76313Naphthoxyacetic acidHCID 2596681-Bromo-4-phenylbutaneHCID 178418339Butyllithium

Product 1

HCID 19851392(+/-)-2-(1-Naphthoxy)-6-phenylhexanoic acidYield 23.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 5 ml of dry tetrahydrofuran and 0.26 g of 50% sodium hydride (suspension in oil) were added 0.7 ml of diisopropylamine and 1.0 g of 1-naphthoxyacetic acid with stirring under an argon atmosphere under ice-cooling. The mixture was heated for 30 minutes at 50° C., and then heated under reflux for 15 minutes. After cooling below 5° C., to the reaction mixture was added dropwise 3.5 ml of n-butyllithium (as a 1.6 mole hexane solution), the mixture was stirred below 10° C. for 20 minutes, and then warmed for 20 minutes at 30° C. After cooling below 5° C. again, 1.00 g of 4-phenylbutyl bromide was added to the reaction mixture. The mixture was stirred for 30 minutes at below 5° C., and then warmed for 1 hour at 30° C. with stirring. After cooling, the reaction mixture was washed with diethyl ether to remove neutral materials. The aqueous layer was acidified by adding concentrated hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography (eluent: benzene) to obtain 0.37 g of (±)-2-(1-naphthoxy)-6-phenylhexanoic acid as colorless crystals.

Workup

  1. temperaturecooling
  2. temperatureheated
  3. temperatureunder reflux for 15 minutes
  4. temperatureAfter cooling below 5° C., to the reaction mixture
  5. stirringwas stirred below 10° C. for 20 minutes
  6. temperaturewarmed for 20 minutes at 30° C
  7. temperatureAfter cooling below 5° C. again
  8. stirringThe mixture was stirred for 30 minutes at below 5° C.
  9. temperaturewarmed for 1 hour at 30° C.
  10. stirringwith stirring
  11. temperatureAfter cooling
  12. washthe reaction mixture was washed with diethyl ether
  13. customto remove neutral materials
  14. additionby adding concentrated hydrochloric acid
  15. extractionextracted with ethyl acetate
  16. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  17. dry with materialdried over anhydrous magnesium sulfate
  18. concentrationconcentrated under reduced pressure
  19. customThe residue was purified by silica gel flash column chromatography (eluent: benzene)

Sources & evidence

ORD record
ord-c165ff0202274dcba46f98b528303fae
Source dataset
uspto-grants-1989_09
Patent number
US04863904

Reaction notes

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