Sodium Iodide → 2-Cyclopropylmethyl-5-iodo-7-methyl-2,3-dihydro-isoindol-1-one

HRID 252071

Reaction equation

HRID 252071 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][CH:14]1[CH2:16][CH2:15]1)[CH2:5]2.CN[C@@H]1CCCC[C@H]1NC.[I-:27].[Na+]>C(O)CCC.C(OCC)(=O)C.[Cu]I>[CH:14]1([CH2:13][N:6]2[CH2:5][C:4]3[C:8](=[C:9]([CH3:11])[CH:10]=[C:2]([I:27])[CH:3]=3)[C:7]2=[O:12])[CH2:16][CH2:15]1

Participants

7

Reactant 3

HCID 5238Sodium IodideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 579494565-Bromo-2-cyclopropylmethyl-7-methyl-2,3-dihydro-isoindol-1-one

Product 1

HCID 576722522-Cyclopropylmethyl-5-iodo-7-methyl-2,3-dihydro-isoindol-1-oneYield 92%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 2631-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 5-Bromo-7-methyl-2-cyclopropylmethyl-2,3-dihydro-isoindol-1-one (1.0 g, 3.56 mmol) in butanol (10 ml), (1R,2R)-N,N′-dimethylcyclohexane-1,2-diamine (204 mg, 1.42 mmol), copper(I) iodide (140 mg, 0.714 mmol) and sodium iodide (1.08 g, 14.3 mmol) were added. The resulting mixture was stirred at 120° C. overnight. After cooling, the mixture was diluted with ethyl acetate, washed with water, brine, dried over anhydrous sodium sulphate, filtered, concentrated. Column chromatography (30% EtOAc/Hexanes) provided the title compound (1.07 g, 92%) as a colourless solid. 1H NMR (300 MHz, CDCl3): δ 7.65 (s, 1H), 7.59 (s, 1H), 4.42 (s, 2H), 3.46-3.44 (d, 2H), 2.70 (s, 3H), 1.04-1.02 (m, 1H), 0.61-0.57 (m, 2H), 0.34-0.31 (m, 2H)

Workup

  1. temperatureAfter cooling
  2. washwashed with water, brine
  3. dry with materialdried over anhydrous sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c7538003ab6a4e1c88550d3a9d27caef
Source dataset
uspto-grants-2011_01
Patent number
US07868008B2

Linked notes

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