Methyl iodide → HCID 59438472, compound

HRID 1950913Notes

Reaction equation

HRID 1950913 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:13]1[O:14][CH2:15][C:16]([CH3:19])([CH3:18])[N:17]=1.[CH:20]([N-]C(C)C)(C)C.[Li+].IC>C1COCC1>[CH3:1][O:2][C:3]1[C:8]([CH3:20])=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:6]=[CH:5][C:4]=1[C:13]1[O:14][CH2:15][C:16]([CH3:19])([CH3:18])[N:17]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 594385352-(2-Methoxy-4-trifluoromethyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole

Product 1

HCID 59438472HCID 59438472, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5.465 g (20 mmol) 2-(2-methoxy-4-trifluoromethyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole in 60 ml dry THF were added at <−60° C. 11.0 ml (22 mmol) lithium diisopropylamide solution 2M in THF/heptanes/ethylbenzene and the mixture stirred for 1.5 h at <−60° C. To the resulting dark brown solution were added 2.5 ml (40 mmol) iodomethane drop wise over 10 min (exothermal, Ti<−48° C.). The resulting light brown solution was stirred at <−50° C. for 2.5 h then quenched with sat. aq. NH4Cl solution and extracted three times with tert-butyl methyl ether. The combined organic phases were washed 3× with brine, dried over Na2SO4, filtered and evaporated: 7.002 g yellow solid: which was purified by flash-chromatography on silica gel with heptane and 5 to 10% AcOEt over 25 min and heptane/AcOEt 90:10 for 20 min. 2-(2-Methoxy-3-methyl-4-trifluoromethyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole was obtained as light yellow oil: MS (ISP): 288.12 ((M+H)+).

Workup

  1. custom(exothermal, Ti<−48° C.)
  2. customthen quenched with sat. aq. NH4Cl solution
  3. extractionextracted three times with tert-butyl methyl ether
  4. washThe combined organic phases were washed 3× with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. custom7.002 g yellow solid: which was purified by flash-chromatography on silica gel with heptane and 5 to 10% AcOEt over 25 min
  9. waitheptane/AcOEt 90:10 for 20 min

Sources & evidence

ORD record
ord-ca7047bce8fa486fab3362f94ea5f9f3
Source dataset
uspto-grants-2013_03
Patent number
US08404673B2

Reaction notes

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