Potassium Fluoride → HCID 86713146, compound

HRID 713628Notes

Reaction equation

HRID 713628 reaction equation
[CH3:1][CH:2]1[CH:6]([CH3:7])[O:5][C:4]2([CH2:12][C:11]([CH3:17])([C:13]([F:16])([F:15])[F:14])[C:10](/[CH:19]=[CH:20]/[Sn](CCCC)(CCCC)CCCC)([OH:18])[C:9]([CH3:34])=[CH:8]2)[O:3]1.[CH:35]1(/[C:38](/I)=[CH:39]/[C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:37][CH2:36]1.[F-].[K+]>CC#N.CC#N.Cl[Pd]Cl.O1CCCC1>[CH:35]1(/[C:38](/[CH:20]=[CH:19]/[C:10]2([OH:18])[C:11]([CH3:17])([C:13]([F:16])([F:14])[F:15])[CH2:12][C:4]3([O:5][CH:6]([CH3:7])[CH:2]([CH3:1])[O:3]3)[CH:8]=[C:9]2[CH3:34])=[CH:39]/[C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:37][CH2:36]1

Participants

6

Reactant 3

HCID 522689Potassium FluorideHCID 70873452HCID 70873452, compoundHCID 86713147HCID 86713147, compound

Product 1

HCID 86713146HCID 86713146, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Under argon, 2,3,7,9-tetramethyl-8-[(E)-2-(tributylstannyl)vinyl]-9-(trifluoromethyl)-1,4-dioxaspiro[4.5]dec-6-en-8-ol (150 mg, 0.25 mmol) and ethyl (2Z)-3-cyclopropyl-3-iodoacrylate (67 mg, 0.25 mmol) in a round-bottom flask that had been dried by heating were dissolved in abs. tetrahydrofuran (4 ml), dichlorobis(acetonitrile)palladium(II) (3 mg, 0.01 mmol) was added and the mixture was stirred at room temperature for 3 h. After the addition of potassium fluoride solution, the reaction mixture was stirred further at room temperature overnight. The aqueous phase was then repeatedly extracted thoroughly with diethyl ether, and the combined organic phases were then dried over magnesium sulfate, filtered and concentrated under reduced pressure. By final column chromatography purification of the resulting crude product (ethyl acetate/heptane gradient), ethyl (2Z,4E)-3-cyclopropyl-5-[8-hydroxy-2,3,7,9-tetramethyl-9-(trifluoromethyl)-1,4-dioxaspiro[4.5]dec-6-en-8-yl]penta-2,4-dienoate (40 mg, 36% of theory) was obtained in the form of a colorless oil. 1H-NMR (400 MHz, CDCl3 δ, ppm) 7.80/7.78 (d, 1H), 6.40/6.38 (d, 1H), 5.62/5.60 (s, 1H), 5.52/5.44 (s, 1H), 4.28/3.63 (m, 2H), 4.18 (q, 2H), 2.52/2.41 (d, 1H), 2.03/1.94 (d, 1H), 2.00 (br. s, 1H, OH), 1.72/1.69 (s, 3H), 1.62/1.55 (m, 1H), 1.40-1.34 (m, 3H), 1.29-1.17 (m, 6H), 0.92 (t, 3H), 0.83 (m, 2H), 0.58 (m, 2H).

Workup

  1. temperatureby heating
  2. dissolutionwere dissolved in abs
  3. stirringthe reaction mixture was stirred further at room temperature overnight
  4. extractionThe aqueous phase was then repeatedly extracted thoroughly with diethyl ether
  5. dry with materialthe combined organic phases were then dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customBy final column chromatography purification of the resulting crude product (ethyl acetate/heptane gradient)

Sources & evidence

ORD record
ord-0636b303d60641eaad4a1436433111e7
Source dataset
uspto-grants-2015_11
Patent number
US09185914B2

Reaction notes

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