HCID 67402411, compound → HCID 67403359, compound

HRID 906199Notes

Reaction equation

HRID 906199 reaction equation
[NH2:1][C:2]1[C:3](I)=[CH:4][C:5]([C:12]([F:15])([F:14])[F:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[NH2:17][C:18]1C(C(F)(F)F)=C(C=CC=1I)C(OC)=O>CN(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>[NH2:1][C:2]1[C:3]([C:18]#[N:17])=[CH:4][C:5]([C:12]([F:15])([F:14])[F:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

6

Reactant 2

HCID 67402411HCID 67402411, compoundHCID 67403170HCID 67403170, compound

Product 1

HCID 67403359HCID 67403359, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 5-amino-4-iodo-2-(trifluoromethyl)benzoate (major) and methyl 3-amino-4-iodo-2-(trifluoromethyl)benzoate (minor) in a 4:1 ratio (prepared in Example 51 Step 4) (1.08 g, 3.13 mmol) was dissolved in DMF (17 mL), and the mixture was sparged with nitrogen for 15 minutes. Zinc cyanide (257 mg, 2.19 mmol) and tetrakis(triphenylphosphine)palladium(0) (362 mg, 0.313 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. The aqueous wash was back-extracted with ethyl acetate (2×). The combined organic portion was washed with 10% lithium chloride and brine, was dried over sodium sulfate then filtered and concentrated to afford a residue which was purified by column chromatography (silica gel, 30-50% ethyl acetate in hexanes) to afford pure methyl 5-amino-4-cyano-2-(trifluoromethyl)benzoate (556 mg, 2.28 mmol, 73% yield). 1H NMR (400 MHz, CDCl3): δ 7.76 (s, 1H), 7.10 (s, 1H), 4.88 (br s, 2H), 3.93 (s, 3H); GCMS for C10H7F3N2O2: 244 (M+).

Workup

  1. customin a 4:1 ratio (prepared in Example 51 Step 4) (1.08 g, 3.13 mmol)
  2. customthe mixture was sparged with nitrogen for 15 minutes
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. filtrationwas filtered through celite
  5. washThe filter cake was washed with ethyl acetate
  6. washthe filtrate was washed with 5% lithium chloride
  7. washThe aqueous wash
  8. extractionwas back-extracted with ethyl acetate (2×)
  9. washThe combined organic portion was washed with 10% lithium chloride and brine
  10. dry with materialwas dried over sodium sulfate
  11. filtrationthen filtered
  12. concentrationconcentrated
  13. customto afford a residue which
  14. customwas purified by column chromatography (silica gel, 30-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c45b0f3ea5b74aa78ae5c52d5a7012d1
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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