Hydrochloric Acid → ethyl (2E,4E)-5-(1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-(trifluoromethyl)penta-2,4-dienoate

HRID 713621Notes

Reaction equation

HRID 713621 reaction equation
[OH:1][C:2]1(/[CH:17]=[CH:18]/[C:19](/[C:26]([F:29])([F:28])[F:27])=[CH:20]\[C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:13]([CH3:15])([CH3:14])[CH2:12][C:5]2(OC(C)C(C)[O:6]2)[CH:4]=[C:3]1[CH3:16].Cl.O>CC(C)=O>[OH:1][C:2]1(/[CH:17]=[CH:18]/[C:19](/[C:26]([F:27])([F:28])[F:29])=[CH:20]\[C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:13]([CH3:14])([CH3:15])[CH2:12][C:5](=[O:6])[CH:4]=[C:3]1[CH3:16]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 86713142ethyl (2E,4E)-5-(8-hydroxy-2,3,7,9,9-pentamethyl-1,4-dioxaspiro[4.5]dec-6-en-8-yl)-3-(trifluoromethyl)penta-2,4-dienoate

Product 1

HCID 86713143ethyl (2E,4E)-5-(1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-(trifluoromethyl)penta-2,4-dienoateYield 64.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Ethyl (2E,4E)-5-(8-hydroxy-2,3,7,9,9-pentamethyl-1,4-dioxaspiro[4.5]dec-6-en-8-yl)-3-(trifluoromethyl)penta-2,4-dienoate (150 mg, 0.36 mmol) was dissolved in acetone (5 ml) under argon in a round-bottom flask, and 10% strength hydrochloric acid was added. The resulting reaction solution was stirred at room temperature for 40 minutes, and water was then added. After removing acetone under reduced pressure, the aqueous phase was extracted repeatedly with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the resulting crude product (ethyl acetate/heptane gradient), ethyl (2E,4E)-5-(1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-(trifluoromethyl)penta-2,4-dienoate (80 mg, 61% of theory) was obtained in the form of a colorless oil. 1H-NMR (400 MHz, CDCl3 δ, ppm) 7.55 (d, 1H), 6.37 (d, 1H), 6.33 (s, 1H), 5.97 (s, 1H), 4.25 (q, 2H), 2.47 (d, 1H), 2.34 (d, 1H), 1.92 (s, 3H), 1.90 (br. s, 1H, OH), 1.33 (t, 3H), 1.11 (s, 3H), 1.02 (s, 3H).

Workup

  1. customThe resulting reaction solution
  2. customAfter removing acetone under reduced pressure
  3. extractionthe aqueous phase was extracted repeatedly with dichloromethane
  4. dry with materialThe combined organic phases were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customBy column chromatography purification of the resulting crude product (ethyl acetate/heptane gradient)

Sources & evidence

ORD record
ord-d4f5ba8ab9a64e378046b71beb8ebf2c
Source dataset
uspto-grants-2015_11
Patent number
US09185914B2

Reaction notes

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