Toluene → (5-Vinyl-1,3-dihydro-isoindol-2-yl)-methanone

HRID 2060164Notes

Reaction equation

HRID 2060164 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([C:11](C1C=C(C(C)C)C(OC)=CC=1OC)=[O:12])[CH2:5]2.C([O-])([O-])=O.[Na+].[Na+].[C:32]1(C)C=CC=C[CH:33]=1>CO.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:32]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([CH:11]=[O:12])[CH2:5]2)=[CH2:33]

Participants

7

Reactant 3

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 57830188(5-Bromo-1,3-dihydro-isoindol-2-yl)-(5-isopropyl-2,4-dimethoxyphenyl)methanone

Product 1

HCID 86616299(5-Vinyl-1,3-dihydro-isoindol-2-yl)-methanone

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

To (5-bromo-1,3-dihydro-isoindol-2-yl)-(5-isopropyl-2,4-dimethoxyphenyl)methanone (2.2 g, 5.44 mmol), and 2-vinyl-4,4,5,5-tetramethyl-1,3,2-dioxaboralane (1.2 ml, 6.53 mmol) in MeOH (25 ml) and toluene (25 ml) was added Na2CO3 in water (25 ml). The reaction was degassed, Pd(PPh3)4 (0.38 g, 0.05 mmol) added then heated at 80° C. overnight. The reaction was worked up by adding water and extracting with EtOAc (×3). The combined organic layers were washed with brine and dried over MgSO4. The product was filtered and evaporated to dryness then purified by flash column chromatography, gradient elution (ether:petrol) to yield 5-isopropyl-2,4-dimethoxy-phenyl)-(5-vinyl-1,3-dihydro-isoindol-2-yl)-methanone as a yellow oil (1.6 g). 1H NMR (Me-d3-OD) 7.47-7.15 (3H, m), 7.15 (1H, s), 6.82-6.72 (1H, m), 6.71 (1H, s), 5.79 (1H, dd), 5.24 (1H, dd), 4.90 (2H, d), 4.64 (2H, d), 3.93 (3H, s), 3.91 (3H, s), 3.27 (1H, sept), 1.23 (6H, d). MS: [M+H]+ 352.

Workup

  1. customThe reaction was degassed
  2. extractionextracting with EtOAc (×3)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationThe product was filtered
  6. customevaporated to dryness
  7. customthen purified by flash column chromatography, gradient elution (ether:petrol)

Sources & evidence

ORD record
ord-8581ae4968c24335959773d70b36f9f8
Source dataset
uspto-grants-2012_10
Patent number
US08277807B2

Reaction notes

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