Hydrochloric Acid → HCID 21193733, compound

HRID 1871538Notes

Reaction equation

HRID 1871538 reaction equation
[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].C([Li])CCC.[CH:17]1([O:22][C:23]2[CH:24]=[C:25]([CH:28]=[CH:29][C:30]=2[O:31][CH3:32])[CH:26]=[O:27])[CH2:21][CH2:20][CH2:19][CH2:18]1.Cl>C1COCC1.CCOCC.O>[CH:17]1([O:22][C:23]2[CH:24]=[C:25]([CH:26]([OH:27])[CH2:7][C:5](=[O:6])[CH2:4][C:3]([O:9][CH2:10][CH3:11])=[O:8])[CH:28]=[CH:29][C:30]=2[O:31][CH3:32])[CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 27358933-Cyclopentyloxy-4-methoxybenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 21193733HCID 21193733, compoundYield 53%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (6.0 g of 60% sodium hydride in mineral oil, 0.15 mol) was placed in a 3-neck flask equiped with a mechanical stirrer under nitrogen and washed twice with hexanes. THF (200 mL) was added and the mixture was cooled in an ice bath. Ethyl acetoacetate (17.6 g, 0.135 mol) was added dropwise and the mixture was stirred for 10 minutes after the addition. Butyllithium (0.35 mol, 84 mL of 1.6 M solution in hexanes) was added dropwise to give an orange solution. A solution of 3-cyclopentyloxy-4-methoxybenzaldehyde (29.6 g, 0.135 mol) in THF (100 mL) was added dropwise. After 10 minutes, the cold solution was treated with concentrated hydrochloric acid (26 mL, 0.29 mol), water (65 mL) and ether (500 mL). The ether layer was separated and washed with saturated brine (3×300 mL). The ether was evaporated to give 46.5 g of crude title compound. The crude product was dissolved in a small amount of 30% methylene chloride/hexanes and purified by chromatography over 400 g of flash chromatography silica gel. Elution with methylene chloride/hexane mixtures removed 9 g of starting aldehyde. Elution with 1% methanol/methylene chloride afforded the ethyl 5-(3-cyclopentyloxy-4-methoxyphenyl)-3-oxo-5-hydroxypentanoate (25.0 g, 53%) as an oil.

Workup

  1. customequiped with a mechanical stirrer under nitrogen
  2. washwashed twice with hexanes
  3. additionTHF (200 mL) was added
  4. temperaturethe mixture was cooled in an ice bath
  5. additionafter the addition
  6. customto give an orange solution
  7. waitAfter 10 minutes
  8. customThe ether layer was separated
  9. washwashed with saturated brine (3×300 mL)
  10. customThe ether was evaporated
  11. customto give 46.5 g of crude title compound
  12. custompurified by chromatography over 400 g of flash chromatography silica gel
  13. washElution with methylene chloride/hexane
  14. custommixtures removed 9 g of starting aldehyde
  15. washElution with 1% methanol/methylene chloride

Sources & evidence

ORD record
ord-5e7f2d702a4240eb962df93edf3ededb
Source dataset
uspto-grants-2000_08
Patent number
US06103749

Reaction notes

Loading…