Lithium diisopropylamide → 1-(4-(4-Bromo-3,5-dimethoxyphenyl)oxazol-2-yl)-2-methoxy-2-(4-morpholinophenyl)-ethanone

HRID 2359153Notes

Reaction equation

HRID 2359153 reaction equation
[Br:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2[N:11]=[CH:12][O:13][CH:14]=2)=[CH:4][C:3]=1[O:15][CH3:16].[Li+].CC([N-]C(C)C)C.CON(C)[C:28](=[O:44])[CH:29]([O:42][CH3:43])[C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[CH:32][CH:31]=1>C1COCC1>[Br:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2[N:11]=[C:12]([C:28](=[O:44])[CH:29]([O:42][CH3:43])[C:30]3[CH:31]=[CH:32][C:33]([N:36]4[CH2:37][CH2:38][O:39][CH2:40][CH2:41]4)=[CH:34][CH:35]=3)[O:13][CH:14]=2)=[CH:4][C:3]=1[O:15][CH3:16]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 58431993N,2-dimethoxy-N-methyl-2-(4-morpholinophenyl)acetamideHCID 584321254-(4-Bromo-3,5-dimethoxyphenyl)oxazole

Product 1

HCID 584321301-(4-(4-Bromo-3,5-dimethoxyphenyl)oxazol-2-yl)-2-methoxy-2-(4-morpholinophenyl)-ethanoneYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-15 °C

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]+.

Workup

  1. temperaturethen cooled to −20° C
  2. temperatureto slowly warm to room temperature
  3. stirringstirred for a total of 21 hours
  4. customThe reaction mixture was quenched with H2O
  5. extractionextracted with EtOAc
  6. washThe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customPurification by chromatography (50-60% EtOAc-hexanes)

Sources & evidence

ORD record
ord-2fe02f27446949488752b50244d142f6
Source dataset
uspto-grants-2014_04
Patent number
US08685975B2

Reaction notes

Loading…