Tetrahydrofuran → 4-Amino-6-(4-ethoxy-3-trifluoromethyl-phenyl)-3-nitro-pyridine-2-carbonitrile

HRID 2246429Notes

Reaction equation

HRID 2246429 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([C:9]#[N:10])[C:3]=1[N+:11]([O-:13])=[O:12].[CH2:14]([O:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][C:18]=1[C:26]([F:29])([F:28])[F:27])[CH3:15].C(=O)([O-])[O-].[K+].[K+].C1COCC1>C(OCC)C>[NH2:1][C:2]1[CH:7]=[C:6]([C:20]2[CH:21]=[CH:22][C:17]([O:16][CH2:14][CH3:15])=[C:18]([C:26]([F:27])([F:29])[F:28])[CH:19]=2)[N:5]=[C:4]([C:9]#[N:10])[C:3]=1[N+:11]([O-:13])=[O:12]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 445581844-Ethoxy-3-(trifluoromethyl)benzeneboronic acidHCID 552704134-Amino-6-chloro-3-nitro-pyridine-2-carbonitrile

Product 1

HCID 589381224-Amino-6-(4-ethoxy-3-trifluoromethyl-phenyl)-3-nitro-pyridine-2-carbonitrileYield 50.7%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
150 °C

Procedure

A stirred mixture 4-amino-6-chloro-3-nitro-pyridine-2-carbonitrile (1 g, 5.04 mmol), 4-ethoxy-3-trifluoromethylphenylboronic acid (1.33 g, 6.04 mmol), tetrakis-(triphenylphosphine)palladium(0) (˜500 mg,10 mol %), potassium carbonate (2.09 g, 15.12 mmol) and THF (10 ml) was degassed under a stream of nitrogen before heating in the “Smith” microwave at 150° C. for 10 minutes. The crude mixture was concentrated under reduced pressure to remove THF before partitioning between ethyl acetate and water. The organic layer was separated, dried over sodium sulfate and concentrated under reduced pressure to give a dark brown oil. Trituration with diethylether gave a light brown solid which was filtered and dried under a stream of air to afford 4-amino-6-(4-ethoxy-3-trifluoromethyl-phenyl)-3-nitro-pyridine-2-carbonitrile (900 mg). 1H NMR (DMSO): δ 8.25-8.1 (m, 3H), 7.63 (s, 1H), 7.44 (d, 2H), 4.27 (q, 2H), 1.38 (t, 3H).

Workup

  1. concentrationThe crude mixture was concentrated under reduced pressure
  2. customto remove THF
  3. custombefore partitioning between ethyl acetate and water
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a dark brown oil
  8. filtrationwas filtered
  9. customdried under a stream of air

Sources & evidence

ORD record
ord-7bbb401473a3477ea254cd62539f84bb
Source dataset
uspto-grants-2010_03
Patent number
US07687515B2

Reaction notes

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