Sodium Cyanide → 7-methyl-1-oxo-2-(4-chloro-benzyl)-2,3-dihydro-1H-isoindole-5-carbonitrile

HRID 2427709Notes

Reaction equation

HRID 2427709 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][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[CH2:5]2.[C-:21]#[N:22].[Na+].CCCCCC.CCOC(C)=O>C(#N)C.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.[Cu]I>[CH3:11][C:9]1[CH:10]=[C:2]([C:21]#[N:22])[CH:3]=[C:4]2[C:8]=1[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[CH2:5]2

Participants

7

Reactant 3

HCID 8929Sodium CyanideHCID 116818375-Bromo-7-methyl-2-(4-chloro-benzyl)-2,3-dihydro-isoindol-1-oneHCID 21226206Ethyl acetate hexane

Product 1

HCID 668729117-methyl-1-oxo-2-(4-chloro-benzyl)-2,3-dihydro-1H-isoindole-5-carbonitrileYield 531.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-bromo-7-methyl-2-(4-chloro-benzyl)-2,3-dihydro-isoindol-1-one (0.205 g, 0.59 mmol), Pd(PPh3)4 (0.070 g, 0.06 mmol), sodium cyanide (0.038 g, 0.8 mmol), and CuI (0.013 g, 0.07 mmol) in acetonitrile (3 mL) was stirred at 80° C. for 18 h. Workup and silica gel column chromatography using 2:1 hexanes-ethyl acetate (typically 2:1 hexane-EtOAc) afforded 7-methyl-1-oxo-2-(4-chloro-benzyl)-2,3-dihydro-1H-isoindole-5-carbonitrile (0.93 g, 54%). 1H NMR (300 MHz, CDCl3): δ (ppm) 2.78 (s, 3H), 4.26 (s, 2H), 4.65 (s, 2H), 7.24 (d, 2H), 7.33 (d, 2H), 7.52 (d, 2H). GC-MS: m/z 296 (M)+, 261 (M−35)+.

Sources & evidence

ORD record
ord-8f5f1f906d9d42e4a4a35a8e95b6a7f3
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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