Dimethylformamide → HCID 67252950, compound

HRID 2427768Notes

Reaction equation

HRID 2427768 reaction equation
I[C:2]1[CH:3]=[C:4]([O:24][CH:25]([F:27])[F:26])[CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=1)[CH2:7]2.[CH3:28][N:29](C=O)C>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Zn].[C-]#N.[Zn+2].[C-]#N>[F:26][CH:25]([F:27])[O:24][C:4]1[CH:3]=[C:2]([C:28]#[N:29])[C:10]2[C:9](=[O:11])[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)[CH2:7][C:6]=2[CH:5]=1

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 67252112HCID 67252112, compound

Product 1

HCID 67252950HCID 67252950, compoundYield 20%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 7-iodo-2-(4-trifluoromethoxy-benzyl)-5-difluoromethoxy-2,3-dihydro-isoindolone (0.125 g, 0.25 mmol), PdCl2(dppf)2 (0.009 g, 0.012 mmol), zinc (0.002 g, 0.03 mmol), zinc cyanide (0.035 g, 0.3 mmol) and DMF (3 mL) was stirred at 150° C. for 1 h. The reaction mixture was cooled to room temperature, dissolved in ethyl acetate (50 mL) and washed with water. Combined organic layer was dried (MgSO4), filtered and concentrated. Silica gel column chromatography using 10:1 hexane-ethyl acetate afforded 6-difluoromethoxy-3-oxo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-1H-isoindole-4-carbonitrile (0.02 g, 20%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.32 (s, 2H), 4.80 (s, 2H), 6.60 (t, 1H), 6.87 (s, 1H), 7.21 (d, 2H), 7.37 (d, 2H), 7.42 (s, 1H), 7.53 (s, 1H). GC-MS: m/z 398 (M)+, 313 (M−85)+

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water
  3. dry with materialCombined organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-ad97afae4d264fba8fcb05c927b06c9c
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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