Reaction #84772

Reaction equation

N,2-dimethoxy-N-methyl-2-(4-morpholinophenyl)acetamide

4-(4-bromo-3,5-dimethoxyphenyl)oxazole

LDA

→

1-(4-(4-bromo-3,5-dimethoxyphenyl)oxazol-2-yl)-2-methoxy-2-(4-morpholinophenyl)-ethanone

Yield 34.0%

Solvents

THF

THF

Conditions

Workup

1. 1
   Temperaturethen cooled to −20° C
2. 2
   Temperatureto slowly warm to room temperature
3. 3
   workup.STIRRINGstirred for a total of 21 hours
4. 4
   OtherThe reaction mixture was quenched with H2O
5. 5
   Extractionextracted with EtOAc
6. 6
   WashThe combined organics were washed with brine
7. 7
   Dryingdried over Na2SO4
8. 8
   Concentrationconcentrated
9. 9
   OtherPurification by chromatography (50-60% EtOAc-hexanes)

Procedure

To a −20° C. solution of 4-(4-bromo-3,5-dimethoxyphenyl)oxazole (0.158 g, 0.56 mmol) in anhydrous THF (2 mL) in an oven-dried flask under argon was added a solution of LDA (2.0 M in THF/heptane/ethylbenzene; 0.37 mL, 0.74 mmol) dropwise. The mixture was stirred at −20 to −10° C. for 50 min then cooled to −20° C. A solution of N,2-dimethoxy-N-methyl-2-(4-morpholinophenyl)acetamide (0.245 g, 0.83 mmol) in anhydrous THF (3 mL) was added then the mixture was allowed to slowly warm to room temperature and stirred for a total of 21 hours. The reaction mixture was quenched with H2O and extracted with EtOAc. The combined organics were washed with brine, dried over Na2SO4 and concentrated. Purification by chromatography (50-60% EtOAc-hexanes) provided 1-(4-(4-bromo-3,5-dimethoxyphenyl)oxazol-2-yl)-2-methoxy-2-(4-morpholinophenyl)-ethanone as a yellow solid (0.097 g, 34% yield). MS: m/z 517.1 [M+H]+.

Source