Dimethylformamide → Ethyl 2-(5-amino-2-cyano-4-fluorophenyl)acetate

HRID 1257244Notes

Reaction equation

HRID 1257244 reaction equation
[NH2:1][C:2]1[C:3]([F:15])=[CH:4][C:5](Br)=[C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:7]=1.[CH3:16][N:17](C=O)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>[NH2:1][C:2]1[C:3]([F:15])=[CH:4][C:5]([C:16]#[N:17])=[C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:7]=1

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 86713632HCID 86713632, compound

Product 1

HCID 68982767Ethyl 2-(5-amino-2-cyano-4-fluorophenyl)acetateYield 25%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

A solution of Example C5 (3 g, 10.9 mmol) in DMF (50 mL) was treated with ZnCN2 (1.7 g, 16.4 mmol) and Pd(PPh3)4 (1.26 g, 1.09 mmol), sparged with N2 and heated at 100° C. for 12 h. The mixture was cooled to RT, treated with water and extracted with EtOAc (3×). The combined organics were washed with brine (3×), dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/pet ether) to afford ethyl 2-(5-amino-2-cyano-4-fluorophenyl)acetate (600 mg, 25% yield). 1H NMR (400 MHz, CDCl3): δ 7.19 (d, J=2.4 Hz, 1H), 6.67 (d, J=8.4 Hz, 1H), 4.13-4.11 (q, J=6.8 Hz, 2H), 3.66 (s, 2H), 1.23-1.19 (t, J=6.8 Hz, 3H).

Workup

  1. customsparged with N2
  2. temperatureThe mixture was cooled to RT
  3. additiontreated with water
  4. extractionextracted with EtOAc (3×)
  5. washThe combined organics were washed with brine (3×)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (EtOAc/pet ether)

Sources & evidence

ORD record
ord-b3af355249e345a2b718928e1461f443
Source dataset
uspto-grants-2013_06
Patent number
US08461179B1

Reaction notes

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