2-Cyanobenzoic acid → 6-Amino-2,3-dihydro-3,3-dimethyl-1H-isoindol-1-one

HRID 2070873Notes

Reaction equation

HRID 2070873 reaction equation
[CH3:1][C:2]1([CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[NH:3]1.C(C1C=CC=CC=1C(O)=O)#[N:14].C[Li]>O1CCCC1>[NH2:14][C:7]1[CH:6]=[C:5]2[C:10]([C:2]([CH3:12])([CH3:1])[NH:3][C:4]2=[O:11])=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 1380612-Cyanobenzoic acidHCID 105111753,3-dimethyl-2,3-dihydro-1H-isoindol-1-oneHCID 178418348HCID 178418348, compound

Product 1

HCID 592762466-Amino-2,3-dihydro-3,3-dimethyl-1H-isoindol-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

3,3-Dimethylisoindolin-1-one. 2-Cyanobenzoic acid (3 g, 20.39 mmol) was dissolved in tetrahydrofuran (300 mL) and then cooled to −78° C. Methyllithium (127 mL, 204 mmol) was added dropwise and the reaction was slowly warmed to room temperature over 2 hours. The reaction was quenched with brine then extracted twice with ethyl acetate. The combined organics were washed with 1 N HCl, saturated sodium bicarbonate and water, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography to give the desired product. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 8.58-8.69 (m, 1H), 7.53-7.66 (m, 3H), 7.45 (dd, J=1.56, 7.42 Hz, 1H), 1.44 (s, 6H). MS (ESI) m/z 162.2 [M+1]+.

Workup

  1. temperaturethe reaction was slowly warmed to room temperature over 2 hours
  2. customThe reaction was quenched with brine
  3. extractionthen extracted twice with ethyl acetate
  4. washThe combined organics were washed with 1 N HCl, saturated sodium bicarbonate and water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-43bab4b5d91a48e991a276ef4e56640c
Source dataset
uspto-grants-2012_10
Patent number
US08299056B2

Reaction notes

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