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

HRID 2359165
Notes
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Reaction equation

HRID 2359165 reaction equation
[Br:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2[O:11][CH:12]=[CH:13][CH:14]=2)=[CH:4][C:3]=1[O:15][CH3:16].C([N-]C(C)C)(C)C.[Li+].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[O: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)=[CH:13][CH:14]=2)=[CH:4][C:3]=1[O:15][CH3:16]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 584319882-(4-Bromo-3,5-dimethoxyphenyl)furanHCID 58431993N,2-dimethoxy-N-methyl-2-(4-morpholinophenyl)acetamide

Product 1

HCID 584320731-(5-(4-Bromo-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxy-2-(4-morpholinophenyl)ethanoneYield 59%

Reagents, catalysts & solvents 1

HCID 8028
Tetrahydrofuran
Solvent
2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-(4-bromo-3,5-dimethoxyphenyl)furan (0.203 g, 0.72 mmol) in anhydrous THF (2 mL) under argon in an oven-dried flask cooled to −78° C. was added a solution of lithium diisopropylamide (2.0 M in THF/heptane/ethylbenzene; 0.4 mL, 0.8 mmol) dropwise. After stirring for 35 min at −78° C., a solution of N,2-dimethoxy-N-methyl-2-(4-morpholinophenyl)acetamide (0.315 g, 1.1 mmol) in THF (2 mL) was added dropwise. After stirring for 25 min, the mixture was allowed to warm to room temp while stirring for 2 hrs. The reaction was quenched with the addition of saturated aqueous NH4Cl then brine and EtOAc were added. The layers were separated and the organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. Purification by column chromatography (35-65% EtOAc-hexanes) provided an oil that was triturated with MeOH-Et2O (1:1) with sonication. The solid was collected on a Büchner, rinsed with MeOH-Et2O (1:1) and dried in vacuo to give 1-(5-(4-bromo-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxy-2-(4-morpholinophenyl)ethanone as a yellow solid. A second batch was collected from MeOH-Et2O (˜10%) to give additional product (0.220 g total, 59% yield). MS: m/z 516.1 [M+H]+.

Workup

  1. stirringAfter stirring for 25 min
  2. temperatureto warm to room temp
  3. stirringwhile stirring for 2 hrs
  4. customThe reaction was quenched with the addition of saturated aqueous NH4Cl
  5. additionbrine and EtOAc were added
  6. customThe layers were separated
  7. washthe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customPurification by column chromatography (35-65% EtOAc-hexanes)
  11. customprovided an oil that
  12. customwas triturated with MeOH-Et2O (1:1) with sonication
  13. customThe solid was collected on a Büchner
  14. washrinsed with MeOH-Et2O (1:1)
  15. customdried in vacuo

Sources & evidence

ORD record
ord-2ec95ba5b3f1458896e600aede826e61
Source dataset
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08685975B2

Reaction notes

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