Methyl iodide → 2-Methoxycarbonyl-2-methyl-3-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]propionic acid

HRID 1532735Notes

Reaction equation

HRID 1532735 reaction equation
[CH3:1][O:2][C:3]([CH:5]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][C:19]2[N:20]=[C:21]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[O:22][C:23]=2[CH3:24])=[CH:12][CH:11]=1)[C:6]([OH:8])=[O:7])=[O:4].[CH:31]([N-]C(C)C)(C)C.[Li+].CI.[Cl-].[NH4+]>O1CCCC1>[CH3:1][O:2][C:3]([C:5]([CH3:31])([CH2:9][C:10]1[CH:11]=[CH:12][C:13]([O:16][CH2:17][CH2:18][C:19]2[N:20]=[C:21]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[O:22][C:23]=2[CH3:24])=[CH:14][CH:15]=1)[C:6]([OH:8])=[O:7])=[O:4]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 9866203HCID 9866203, compound

Product 1

HCID 220138822-Methoxycarbonyl-2-methyl-3-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]propionic acidYield 112.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-methoxycarbonyl-3-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]propionic acid (4.10 g, 10.0 mmol) obtained in Example 1 in tetrahydrofuran (50 ml) was dropwise added lithium diisopropylamide (1.5 M cyclohexane solution, 15.0 ml, 22.5 mmol) at −78° C. under argon atmosphere. The mixture was stirred at said temperature and methyl iodide (2.5 ml, 40 mmol) was dropwise added. The mixture was stirred at said temperature for 2 hr and 10% aqeuous ammonium chloride (20 ml) was added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (50 ml). The obtained organic layers were combined, washed with saturated brine (10 ml), dried over magnesium sulfate and concentrated under reduced pressure to give the crude title compound (4.78 g).

Workup

  1. customat −78° C.
  2. additionwas dropwise added
  3. stirringThe mixture was stirred
  4. customfor 2 hr
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (50 ml)
  7. washwashed with saturated brine (10 ml)
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9605a43cb43d4566be7c3955f7b2953f
Source dataset
uspto-grants-2001_03
Patent number
US06204277B1

Reaction notes

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