Tetrahydrofuran → 4-([1,1'-Biphenyl]-2-yl)-2-cyclopropyl-1H-indene

HRID 923733Notes

Reaction equation

HRID 923733 reaction equation
[C:1]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH:9]=[C:10](Br)[CH2:11]2.[CH:23]1([Mg]Br)[CH2:25][CH2:24]1.O1CCCC1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.C1(C)C=CC=CC=1>[C:1]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH:9]=[C:10]([CH:23]1[CH2:25][CH2:24]1)[CH2:11]2

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 1178179484-([1,1'-Biphenyl]-2-yl)-2-bromo-1H-indeneHCID 178418630HCID 178418630, compound

Product 1

HCID 1237470284-([1,1'-Biphenyl]-2-yl)-2-cyclopropyl-1H-indeneYield 37%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of compound 9 (10 g, 28.8 mmol, 1 equiv) and anhydrous toluene (100 mL) was treated with bis(triphenylphosphine)-palladium(II)dichloride (2.35 g, 2.9 mmol, 0.1 equiv). After stirring for 10 minutes, 0.5 M cyclopropylmagnesium bromide in tetrahydrofuran (300 mL, 149.7 mmol, 5.2 equiv) was added dropwise. The reaction was heated at 60° C. overnight. Additional bis(triphenylphosphine)-palladium(II)dichloride (2.35 g, 2.9 mmol, 0.1 equiv) was added and the reaction heated at 60° C. for an additional 24 hours. The reaction was concentrated under reduced pressure and the residue partitioned between water (1 L) and ethyl acetate (1 L). The layers were separated and the aqueous layer washed with ethyl acetate (1 L). The combined organic layers were washed with saturated brine (1 L), dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified over silica gel (200 g) eluting with heptanes to give compound 10 (3.3 g, 37% yield) as a light yellow oil.

Workup

  1. temperaturethe reaction heated at 60° C. for an additional 24 hours
  2. concentrationThe reaction was concentrated under reduced pressure
  3. customthe residue partitioned between water (1 L) and ethyl acetate (1 L)
  4. customThe layers were separated
  5. washthe aqueous layer washed with ethyl acetate (1 L)
  6. washThe combined organic layers were washed with saturated brine (1 L)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified over silica gel (200 g)
  10. washeluting with heptanes

Sources & evidence

ORD record
ord-ce4a078c6d0b41c592d9766392aacb6b
Source dataset
uspto-grants-2016_03
Patent number
US09279024B2

Reaction notes

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