Dimethylformamide → Methyl 3-(4-(3-cyano-5-(trifluoromethyl)phenyl)-oxazol-2-yl)propanoate

HRID 534853Notes

Reaction equation

HRID 534853 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:12]2[N:13]=[C:14]([CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])[O:15][CH:16]=2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH3:23][N:24](C=O)C>C(OCC)(=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:23]([C:2]1[CH:3]=[C:4]([C:12]2[N:13]=[C:14]([CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])[O:15][CH:16]=2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1)#[N:24]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 66750877Methyl 3-(4-(3-bromo-5-(trifluoromethyl)phenyl)oxazol-2-yl)propanoate

Product 1

HCID 66751307Methyl 3-(4-(3-cyano-5-(trifluoromethyl)phenyl)-oxazol-2-yl)propanoateYield 75%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of methyl 3-(4-(3-bromo-5-(trifluoromethyl)phenyl)oxazol-2-yl)-propanoate (Reference Example 44, 0.645 g, 1.71 mmol) and zinc cyanide (0.120 g, 1.02 mmol) in DMF (15.0 mL) was evacuated and purged with nitrogen. To this reaction mixture was added tetrakis(triphenylphosphine)palladium(0) (0.197 g, 0.170 mmol) and the resulting reaction mixture was heated at 100° C. for 8 h. After this time, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with water and saturated sodium chloride, dried (Na2SO4), filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography (silica gel, hexanes/ethyl acetate 4:1) to provide methyl 3-(4-(3-cyano-5-(trifluoromethyl)phenyl)-oxazol-2-yl)propanoate (0.417 g, 75%) as a white solid.

Workup

  1. customwas evacuated
  2. custompurged with nitrogen
  3. customthe resulting reaction mixture
  4. temperatureAfter this time, the reaction mixture was cooled to room temperature
  5. washwashed with water and saturated sodium chloride
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by flash column chromatography (silica gel, hexanes/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-5f8b38ad77e6442ba5e32e506dab163e
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

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