Methyl iodide → Methyl 2-{4-[1-(4-iodophenyl)-1,2-dimethylpropyl]phenoxy}-2-pyridin-2-ylpropanoate

HRID 1025806Notes

Reaction equation

HRID 1025806 reaction equation
[CH:1]([N-]C(C)C)(C)C.[Li+].[I:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([C:21]2[CH:38]=[CH:37][C:24]([O:25][CH:26]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=3)[C:27]([O:29][CH3:30])=[O:28])=[CH:23][CH:22]=2)([CH3:20])[CH:17]([CH3:19])[CH3:18])=[CH:12][CH:11]=1.CN1CCCN(C)C1=O.IC>C1CCCCC1.C1COCC1>[I:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]([C:21]2[CH:22]=[CH:23][C:24]([O:25][C:26]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=3)([CH3:1])[C:27]([O:29][CH3:30])=[O:28])=[CH:37][CH:38]=2)([CH3:20])[CH:17]([CH3:18])[CH3:19])=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2724682Lithium diisopropylamideHCID 58381245Methyl {4-[1-(4-iodophenyl)-1,2-dimethylpropyl]phenoxy}(pyridin-2-yl)acetate

Product 1

HCID 58381237Methyl 2-{4-[1-(4-iodophenyl)-1,2-dimethylpropyl]phenoxy}-2-pyridin-2-ylpropanoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8078CyclohexaneSolvent

Procedure

Lithium diisopropylamide mono (THF) (1.2 equiv. of a 5M solution in cyclohexane) is added to a stirred solution of 5c (1 equiv.) in THF at −78° C. After 15 mins, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1 equiv.) is added followed by iodomethane (1.5 equiv). After 1 h, the reaction mixture is warmed to room temperature and aged until the reaction is deemed complete. The reaction mixture is quenched with saturated aqueous ammonium chloride, poured into saturated aqueous sodium bicarbonate and extracted three times with EtOAc. The combined organic extracts are washed with water, brine, dried (Na2SO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel affords the title compound 5d.

Workup

  1. waitAfter 1 h
  2. customThe reaction mixture is quenched with saturated aqueous ammonium chloride
  3. additionpoured into saturated aqueous sodium bicarbonate
  4. extractionextracted three times with EtOAc
  5. washThe combined organic extracts are washed with water, brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customPurification of the crude residue by flash chromatography on silica gel

Sources & evidence

ORD record
ord-ca194893fd8f4caaae58fc8a94e40389
Source dataset
uspto-grants-2014_05
Patent number
US08729104B2

Reaction notes

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