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

HRID 2412212Notes

Reaction equation

HRID 2412212 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-5e3771851afd4601933b599fc45b9b92
Source dataset
uspto-grants-2014_08
Patent number
US08816087B2

Reaction notes

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