Tetrahydrofuran → HCID 89601123, compound

HRID 514212Notes

Reaction equation

HRID 514212 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]2[C:11](=[O:20])[CH:12]([CH2:17][C:18]#[CH:19])[CH2:13][C:14]=2[O:15][CH3:16])=[C:4]([Cl:21])[CH:3]=1.[C:22](O)(=O)[C:23]#[C:24]C.C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>CCOC(C)=O.ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.CS(C)=O>[Cl:21][C:4]1[CH:3]=[C:2]([C:22]#[C:23][CH3:24])[CH:7]=[C:6]([O:8][CH3:9])[C:5]=1[C:10]1[C:11](=[O:20])[CH:12]([CH2:17][C:18]#[CH:19])[CH2:13][C:14]=1[O:15][CH3:16]

Participants

11

Reactant 5

HCID 8028TetrahydrofuranHCID 685352-Butynoic acidHCID 821241,4-Bis(diphenylphosphino)butaneHCID 2724141Tetrabutylammonium FluorideHCID 89601091HCID 89601091, compound

Product 1

HCID 89601123HCID 89601123, compoundYield 32.1%

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A microwave vial was charged with 2-(4-bromo-2-chloro-6-methoxy-phenyl)-3-methoxy-5-prop-2-ynyl-cyclopent-2-en-1-one (0.147 g, 0.398 mmol), but-2-ynoic acid (0.0368 g, 0.437 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.0141 g, 0.0199 mmol) and 1,4-bis-(diphenylphosphino)butane (0.0170 g, 0.0398 mmol) was sealed and dimethyl sulfoxide (2 mL) was added via syringe followed by tetrabutylammonium fluoride (1 mol/L) in tetrahydrofuran (0.795 mL, 0.795 mmol) and then the solution was heated under microwave irradiation at 110°C. for 40 minutes. The reaction was cooled to room temperature, poured into water (20 ml) and diluted with EtOAc (10 ml). The phases were separated and the aqueous phase was extracted into ethyl acetate (2×10 ml). The combined organic extracts were washed with brine (10 ml), dried over MgSO4, filtered and evaporated to dryness under reduced pressure to give a yellow gum, 230 mg. The residue was dissolved in dichloromethane, adsorbed onto silica and purified by flash chromatography over silica using an EtOAc/isohexane gradient to give the desired compound as a yellow gum (42 mg, 32%) as a seperable mixture of atropisomers with identical spectral data. 1H NMR (400 MHz, CDCl3) δ ppm 7.09 (s, 1H), 6.82 (s, 1H), 3.77 (s, 3H), 3.64 (s, 3H), 3.11-3.09 (m, 1H), 2.74-2.51 (m, 4H), 2.05 (s, 3H), 1.99 (s, 1H).

Workup

  1. customwas sealed
  2. temperatureThe reaction was cooled to room temperature
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted into ethyl acetate (2×10 ml)
  5. washThe combined organic extracts were washed with brine (10 ml)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated to dryness under reduced pressure
  9. customto give a yellow gum, 230 mg
  10. custompurified by flash chromatography over silica using an EtOAc/isohexane gradient

Sources & evidence

ORD record
ord-a8c00c6c66114b8caea6003b347ea0ca
Source dataset
uspto-grants-2015_08
Patent number
US09107415B2

Reaction notes

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