Propionic Acid → ethyl[(1RS,3S)-2,2-dimethyl-6-methylene-3-tetrahydropyranyloxycyclohexyl]acetate

HRID 1789247Notes

Reaction equation

HRID 1789247 reaction equation
[CH3:1][C:2]1([CH3:17])[C@@H:7]([O:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[CH2:6][CH2:5][C:4]([CH2:15]O)=[CH:3]1.C(O)(=O)CC.[C:23]([O-])([O-:28])([O:25][CH2:26][CH3:27])[CH3:24]>>[CH2:26]([O:25][C:23](=[O:28])[CH2:24][CH:3]1[C:4](=[CH2:15])[CH2:5][CH2:6][C@H:7]([O:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[C:2]1([CH3:17])[CH3:1])[CH3:27]

Participants

4

Reactant 3

HCID 1032Propionic AcidHCID 13924113(4S)-3,3-dimethyl-4-tetrahydropyranyloxy-1-hydroxymethylcyclohexeneHCID 86598186Ethyl ortho-acetate

Product 1

HCID 13924115ethyl[(1RS,3S)-2,2-dimethyl-6-methylene-3-tetrahydropyranyloxycyclohexyl]acetateYield 96%

Conditions

Temperature
140 °C

Procedure

Compound (9) (9.45 g, 39.3 mmoles) and propionic acid were dissolved in newly distilled ethyl ortho-acetate (51.0 g, 314 mmoles). The solution was stirred at 140° C. for 6 hours while distilling off ethanol. Ethyl ortho-acetate was removed from the resulting reaction mixture, and the residue was concentrated. After cooling, the residue was diluted with ether. The ether solution was washed with a saturated aqueous solution of sodium hydrogencarbonate and then with an aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (200 g of silica gel; n-hexane/ethyl acetate) to give a compound (10) as a mixture of the (1S,3S)-isomer and (1R,3S)-isomer (11.7 g, 37.7 mmoles, yield 96%).

Workup

  1. distillationwhile distilling off ethanol
  2. customEthyl ortho-acetate was removed from the resulting reaction mixture
  3. concentrationthe residue was concentrated
  4. temperatureAfter cooling
  5. additionthe residue was diluted with ether
  6. washThe ether solution was washed with a saturated aqueous solution of sodium hydrogencarbonate
  7. dry with materialwith an aqueous solution of sodium chloride, dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography (200 g of silica gel; n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-43d5bbdfb3f54ea3b1458d64c905aca6
Source dataset
uspto-grants-1987_08
Patent number
US04687863

Reaction notes

Loading…