Tetrahydrofurfuryl alcohol → 4-(Tetrahydro-furan-2-ylmethoxy)-benzoic acid

HRID 390372Notes

Reaction equation

HRID 390372 reaction equation
[CH2:1]([OH:7])[CH:2]1[O:6][CH2:5][CH2:4][CH2:3]1.O[C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15]C)=[O:14])=[CH:11][CH:10]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[OH-].[Na+]>O1CCCC1.C1(C)C=CC=CC=1.CO>[O:6]1[CH2:5][CH2:4][CH2:3][CH:2]1[CH2:1][O:7][C:9]1[CH:18]=[CH:17][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=1

Participants

9

Reactant 5

HCID 7360Tetrahydrofurfuryl alcoholHCID 7456MethylparabenHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 220568ethyl N-ethoxycarbonyliminocarbamate

Product 1

HCID 37653164-(Tetrahydro-furan-2-ylmethoxy)-benzoic acidYield 31.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tetrahydrofurfuryl alcohol (25 g), methyl 4-hydroxybenzoate (38 g), and triphenylphosphine (72 g) in tetrahydrofuran (300 mL) was slowly added dropwise a solution of diethyl azodicarboxylate in toluene (136 mL, 40% toluene solution) at 0° C., and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and triphenylphosphine oxide was precipitated from ethyl acetate-hexane. Triphenylphosphine oxide was removed by filtration with a glass filter, and the mother liquor was concentrated. The residue was purified by silica gel column chromatography [developing solvent; hexane:ethyl acetate=100:0 (volume ratio)→hexane:ethyl acetate=70:10 (volume ratio)] to give a colorless oil. The obtained colorless oil was dissolved in tetrahydrofuran (200 mL) and methanol (100 mL), 8N aqueous sodium hydroxide solution (100 mL) was added, and the mixture was stirred at 80° C. for 2 hr with heating. The reaction solution was concentrated, cooled to 0° C., neutralized with 6N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound (17 g, yield 31%) as colorless crystals.

Workup

  1. concentrationThe reaction solution was concentrated
  2. customtriphenylphosphine oxide was precipitated from ethyl acetate-hexane
  3. customTriphenylphosphine oxide was removed by filtration with a glass
  4. filtrationfilter
  5. concentrationthe mother liquor was concentrated
  6. customThe residue was purified by silica gel column chromatography [developing solvent; hexane:ethyl acetate=100:0 (volume ratio)→hexane:ethyl acetate=70:10 (volume ratio)]
  7. customto give a colorless oil
  8. stirringthe mixture was stirred at 80° C. for 2 hr
  9. temperaturewith heating
  10. concentrationThe reaction solution was concentrated
  11. temperaturecooled to 0° C.
  12. extractionextracted with ethyl acetate
  13. washThe organic layer was washed with saturated brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-399caded8df946538152093f8604f1e9
Source dataset
uspto-grants-2013_02
Patent number
US08383647B2

Reaction notes

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