Acetonitrile → 7-chloro-1-oxo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-1H-isoindole-5-carbonitrile

HRID 2427707Notes

Reaction equation

HRID 2427707 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1)[CH2:5]2.[C-]#N.[Na+].[C:28](#[N:30])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.CCCCCC.CCOC(C)=O>[Cl:11][C:9]1[CH:10]=[C:2]([C:28]#[N:30])[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]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1)[CH2:5]2

Participants

7

Reactant 3

HCID 6342AcetonitrileHCID 8929Sodium CyanideHCID 117044755-Bromo-7-chloro-2-(4-trifluoromethoxybenzyl)-2,3-dihydroisoindol-1-one

Product 1

HCID 579496207-chloro-1-oxo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-1H-isoindole-5-carbonitrileYield 33%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-bromo-7-chloro-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.349 g, 0.83 mmol), Pd(PPh3)4 (0.317 g, 0.25 mmol), sodium cyanide (0.048 g, 0.946 mmol), CuI (0.016 g, 0.086 mmol), acetonitrile (4 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-chloro-1-oxo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-1H-isoindole-5-carbonitrile (0.100 g, 33%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.32 (s, 2H), 4.79 (s, 2H), 7.20 (d, 2H), 7.35 (d, 2H), 7.58 (s, 1H), 7.70 (s, 1H). GC-MS: m/z 366 (M−1)+, 281 (M−85)+.

Sources & evidence

ORD record
ord-30167fc1bed2458eaf7626059611cbf3
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

Loading…