Sodium Carbonate → Methyl 3-(4-(3-(thiophen-2-yl)-5-(trifluoromethyl)phenyl)oxazol-2-yl)propanoate

HRID 534854Notes

Reaction equation

HRID 534854 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.[S:23]1[CH:27]=[CH:26][CH:25]=[C:24]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.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>[S:23]1[CH:27]=[CH:26][CH:25]=[C:24]1[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

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27339602-Thiopheneboronic acidHCID 66750877Methyl 3-(4-(3-bromo-5-(trifluoromethyl)phenyl)oxazol-2-yl)propanoate

Product 1

HCID 66751326Methyl 3-(4-(3-(thiophen-2-yl)-5-(trifluoromethyl)phenyl)oxazol-2-yl)propanoateYield 32%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of methyl 3-(4-(3-bromo-5-(trifluoromethyl)phenyl)oxazol-2-yl)propanoate (Reference Example 44, 0.454 g, 1.20 mmol), thiophene-2-boronic acid (0.230 g, 1.80 mmol) and sodium carbonate (0.954 g, 9.00 mmol) in toluene (30.0 mL) was evacuated and purged with nitrogen. To this mixture was added tetrakis(triphenylphosphine)palladium(0) (0.208 g, 0.180 mmol) and the resulting reaction mixture was heated at 100° C. for 7 h. After this time, the reaction mixture was cooled to room temperature, quenched with 1.0 M hydrochloric acid (20.0 mL), diluted with ethyl acetate and separated. The organic layer was washed with water and saturated sodium chloride, dried (Na2SO4), filtered and concentrated under reduced pressure. The resultant residue was purified by flash column chromatography (silica gel, hexanes/ethyl acetate 9:1) to provide methyl 3-(4-(3-(thiophen-2-yl)-5-(trifluoromethyl)phenyl)oxazol-2-yl)propanoate (0.145 g, 32%) as a yellow 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. customquenched with 1.0 M hydrochloric acid (20.0 mL)
  6. additiondiluted with ethyl acetate
  7. customseparated
  8. washThe organic layer was washed with water and saturated sodium chloride
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe resultant residue was purified by flash column chromatography (silica gel, hexanes/ethyl acetate 9:1)

Sources & evidence

ORD record
ord-20fa317dcf9b462ab0ffd43c3eca7bef
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

Loading…