Dimethylformamide → HCID 67401806, compound

HRID 906196Notes

Reaction equation

HRID 906196 reaction equation
I[C:2]1[C:11]([NH:12][CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:18]([F:21])([F:20])[F:19])[CH:3]=1.[CH3:22][N:23](C=O)C>[C-]#N.[Zn+2].[C-]#N.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>[C:22]([C:2]1[C:11]([NH:12][CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:18]([F:21])([F:20])[F:19])[CH:3]=1)#[N:23]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 67402961HCID 67402961, compound

Product 1

HCID 67401806HCID 67401806, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

Methyl 4-iodo-5-(pentan-3-ylamino)-2-(trifluoromethyl)benzoate (401 mg, 0.966 mmol) was dissolved in DMF (9 mL) and the mixture was sparged with nitrogen for 15 minutes. Zinc cyanide (79 mg, 0.673 mmol) and tetrakis(triphenylphosphine)palladium(0) (100 mg, 0.086 mmol) were added and the mixture was stirred at 100° C. for 15 h. The reaction mixture was cooled to ambient temperature and was filtered through celite. The filter cake was washed with ethyl acetate and the filtrate was washed with 5% lithium chloride (2×). The combined aqueous wash was back-extracted with ethyl acetate. The combined organic portion was washed with brine, dried over sodium sulfate, then filtered and concentrated to afford a brown semi-solid which was purified by column chromatography (silica gel, 30-50% dichloromethane in hexanes) to afford methyl 4-cyano-5-(pentan-3-ylamino)-2-(trifluoromethyl)benzoate (262 mg, 0.834 mmol, 86% yield) as colorless crystals. 1H NMR (400 MHz, CDCl3): δ 7.71 (s, 1H), 6.96 (s, 1H), 4.76 (d, 1H), 3.94 (s, 3H), 3.49-3.38 (m, 1H), 1.75-1.63 (m, 2H), 1.61-1.49 (m, 2H), 0.96 (t, 6H); GCMS for C15H17F3N2O2: 314 (M+).

Workup

  1. customthe mixture was sparged with nitrogen for 15 minutes
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. filtrationwas filtered through celite
  4. washThe filter cake was washed with ethyl acetate
  5. washthe filtrate was washed with 5% lithium chloride (2×)
  6. washThe combined aqueous wash
  7. extractionwas back-extracted with ethyl acetate
  8. washThe combined organic portion was washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford a brown semi-solid which
  13. customwas purified by column chromatography (silica gel, 30-50% dichloromethane in hexanes)

Sources & evidence

ORD record
ord-23b248a0c3d048b8bcec8dc5abf85d2b
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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