Methyl iodide → HCID 58765671, compound

HRID 860655Notes

Reaction equation

HRID 860655 reaction equation
[CH3:1][O:2][C:3](=[O:18])[CH2:4][C:5]1[N:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][CH:12]=2)[O:8][C:9]=1[CH3:10].[CH:19]([N-]C(C)C)(C)C.[Li+].CI>O1CCCC1>[CH3:1][O:2][C:3](=[O:18])[CH:4]([C:5]1[N:6]=[C:7]([C:11]2[CH:12]=[CH:13][C:14]([Br:17])=[CH:15][CH:16]=2)[O:8][C:9]=1[CH3:10])[CH3:19]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 58765776HCID 58765776, compound

Product 1

HCID 58765671HCID 58765671, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

[2-(4-Bromo-phenyl)-5-methyl-oxazol-4-yl]-acetic acid methyl ester (11.6 g, 37.4 mmol) is dissolved in anhydrous tetrahydrofuran (150 mL) and allowed to stir under nitrogen. Lithium diisopropyl amide solution in tetrahydrofuran (28 mL of 2M soln., 56.1 mmol) is slowly added to the solution at room temperature. This is then heated to 50° C. for 6 hours. The solution is allowed to cool to room temperature and methyl iodide (7.0 mL, 112 mmol) is added in one portion. The mixture is allowed to stir under nitrogen at room temperature overnight. The solution is quenched with a saturated solution of ammonium chloride, diluted with ethyl acetate, and then enough water added to dissolve the solids. The two phases are separated and the organic layer is washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The pure 2-[2-(4-Bromo-phenyl)-5-methyl-oxazol-4-yl]-propionic acid methyl ester (5.57 g, 17.19 mmol) is isolated in 46% yield after column chromatography. The racemic 2-[2-(4-Bromo-phenyl)-5-methyl-oxazol-4-yl)-propionic acid methyl ester is resolved on a Chiralcel OJ column (4.6×250 mm). Eluted with 40% isopropanol in heptane with 0.2% dimethy-ethylamine at 1 mL per minute with detection at 260 nM and concentrated the fractions to provide the pure enantiomer esters (isomer 1, 99.8% ee; isomer 2, 99.4% ee).

Workup

  1. temperatureto cool to room temperature
  2. stirringto stir under nitrogen at room temperature overnight
  3. customThe solution is quenched with a saturated solution of ammonium chloride
  4. additiondiluted with ethyl acetate
  5. additionenough water added
  6. dissolutionto dissolve the solids
  7. customThe two phases are separated
  8. washthe organic layer is washed with water and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-39e167f5bf924b7384e9f7d91a6677fb
Source dataset
uspto-grants-2006_12
Patent number
US07153878B2

Reaction notes

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