Methylparaben → Cyclooctyl 4-hydroxybenzoate

HRID 895762Notes

Reaction equation

HRID 895762 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[CH:12]1(O)[CH2:19][CH2:18]C[CH2:16][CH2:15][CH2:14][CH2:13]1>CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4].C(OCC)(=O)C>[CH:1]1([O:2][C:3](=[O:11])[C:4]2[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:19][CH2:18]1

Participants

5

Reactant 2

HCID 7456MethylparabenHCID 12766Cyclooctanol3×

Product 1

HCID 20812381Cyclooctyl 4-hydroxybenzoateYield 12.6%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalyst2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
180 °C

Procedure

22.82 g (0.15 mol) p-hydroxybenzoic acid methyl ester, 38.47 g (0.30 mol) cyclooctanol and 26 mg (0.1 mmol) tetraisopropyl orthotitanate are placed under argon in a round-bottom flask with distillation bridge. The mixture is stirred and heated to 180° C. within 45 minutes. The pressure is reduced to 800 mbar and over the further course of distillation to 650 mbar. After a further 15 minutes the pressure is increased to 900 mbar and the reaction mixture stirred for a further 2 hours, during which time methanol continues to be removed by distillation. A further 9.62 g (0.075 mol) cyclooctanol and 2 drops of tetraisopropyl orthotitanate are added to the reaction solution and stirred for a further 4 hours at 180° C. It is allowed to cool and the residue is dissolved in 100 ml ethyl acetate and washed repeatedly with distilled water. The organic phase is concentrated to small volume. The crude product is purified by column chromatography (silica gel 60, 0040-0.063 mm, Merck) with an n-hexane/acetone mixture (3:1). The product obtained is freed from adhering cyclooctanol under high vacuum. The white crystalline residue is recrystallised in acetone. 4.70 g (12%) of colourless crystals are obtained.

Workup

  1. distillationThe pressure is reduced to 800 mbar and over the further course of distillation to 650 mbar
  2. temperatureAfter a further 15 minutes the pressure is increased to 900 mbar
  3. stirringthe reaction mixture stirred for a further 2 hours, during which time methanol
  4. customto be removed by distillation
  5. stirringstirred for a further 4 hours at 180° C
  6. temperatureto cool
  7. washwashed repeatedly with distilled water
  8. concentrationThe organic phase is concentrated to small volume
  9. customThe crude product is purified by column chromatography (silica gel 60, 0040-0.063 mm, Merck) with an n-hexane/acetone mixture (3:1)
  10. customThe product obtained
  11. customThe white crystalline residue is recrystallised in acetone

Sources & evidence

ORD record
ord-cae7e9b4cc844619b42cb0fa84089b41
Source dataset
uspto-grants-2005_07
Patent number
US06916899B2

Reaction notes

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