1,2-Dichloroethane → (5-Bromo-1,3-dihydro-isoindol-2-yl)-(5-isopropyl-2,4-dimethoxyphenyl)methanone

HRID 41447Notes

Reaction equation

HRID 41447 reaction equation
[CH:1]([C:4]1[C:5]([O:15][CH3:16])=[CH:6][C:7]([O:13][CH3:14])=[C:8]([CH:12]=1)[C:9]([OH:11])=O)([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[Br:31][C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][CH:40]=1)[CH2:37][NH:36][CH2:35]2>CN(C=O)C>[Br:31][C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][CH:40]=1)[CH2:37][N:36]([C:9]([C:8]1[CH:12]=[C:4]([CH:1]([CH3:2])[CH3:3])[C:5]([O:15][CH3:16])=[CH:6][C:7]=1[O:13][CH3:14])=[O:11])[CH2:35]2

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 147958715-BromoisoindolineHCID 534150805-Isopropyl-2,4-dimethoxybenzoic acid

Product 1

HCID 57830188(5-Bromo-1,3-dihydro-isoindol-2-yl)-(5-isopropyl-2,4-dimethoxyphenyl)methanoneYield 74.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-isopropyl-2,4-dimethoxybenzoic acid (2.45 g, 10.9 mmol), HOBt (1.61 g, 11.9 mmol) and EDC (1.85 g, 11.9 mmol) in anhydrous DMF (33 ml) under N2 was added 5-bromo-2,3-dihydro-1H-isoindole (1.97 g, 9.95 mmol) and stirred at room temperature overnight. The reaction was quenched by diluting with NaOH (1M, aq.) and extracting the product with EtOAc (×2). The combined organic layers were washed with brine and dried over MgSO4. The product was filtered and evaporated to dryness to leave a brown oil. The product was purified by flash column chromatography using gradient elution (ether/petrol) to yield (5-bromo-1,3-dihydro-isoindol-2-yl)-(5-isopropyl-2,4-dimethoxyphenyl)-methanone as a beige solid (3 g). 1H NMR (Me-d3-OD) 7.60-7.13 (3H, m), 7.14 (1H, s), 6.71 (1H, s), 4.89 (2H, d), 4.64 (2H, d), 3.93 (3H, s), 3.90 (3H, s), 3.27 (1H, sept), 1.20 (6H, d). MS: [M+H]+ 404/406.

Workup

  1. customThe reaction was quenched
  2. additionby diluting with NaOH (1M, aq.)
  3. extractionextracting the product with EtOAc (×2)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationThe product was filtered
  7. customevaporated to dryness
  8. customto leave a brown oil
  9. customThe product was purified by flash column chromatography
  10. washelution (ether/petrol)

Sources & evidence

ORD record
ord-12ca1910738541e493cca8a30ba3a080
Source dataset
uspto-grants-2013_09
Patent number
US08530469B2

Reaction notes

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