Sodium Cyanide → 6-methoxy-3-oxo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-1H-isoindole-4-carbonitrile

HRID 2427712Notes

Reaction equation

HRID 2427712 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[C:10](I)[CH:11]=1)[C:8](=[O:13])[N:7]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=1)[CH2:6]2.[C-:26]#[N:27].[Na+]>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>[CH3:1][O:2][C:3]1[CH:11]=[C:10]([C:26]#[N:27])[C:9]2[C:8](=[O:13])[N:7]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=3)[CH2:6][C:5]=2[CH:4]=1

Participants

6

Reactant 2

HCID 8929Sodium CyanideHCID 579493525-Methoxy-7-iodo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

Product 1

HCID 579494456-methoxy-3-oxo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-1H-isoindole-4-carbonitrileYield 68%

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-methoxy-7-iodo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.060 g, 0.13 mmol), Pd(PPh3)4 (0.015 g, 0.013 mmol), sodium cyanide (0.013 g, 0.26 mmol), and CuI (0.003 g, 0.013 mmol) in acetonitrile (5 mL) was stirred at 80° C. for 18 h. Workup and silica gel column chromatography using 2:1 hexanes-ethyl acetate afforded 6-methoxy-3-oxo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-1H-isoindole-4-carbonitrile (0.032 g, 68%). 1H NMR (300 MHz, CDCl3): δ (ppm) 3.89 (s, 3H), 4.36 (s, 2H), 4.77 (s, 2H), 7.10 (s, 1H), 7.17 (d, 2H), 7.25 (s, 1H), 7.36 (d, 2H). GC-MS: m/z 362 (M+.

Sources & evidence

ORD record
ord-c3cc6d0b9cde43a99beb86e065b1c834
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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