Hexachloroethane → 2-Chloro-4-ethyl-5-(4-(trifluoromethyl)phenyl)oxazole

HRID 1672573Notes

Reaction equation

HRID 1672573 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:11]([C:13]1[N:14]=[CH:15][O:16][C:17]=1[C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1)[CH3:12].[Cl:28]C(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[Cl:28][C:15]1[O:16][C:17]([C:18]2[CH:19]=[CH:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=2)=[C:13]([CH2:11][CH3:12])[N:14]=1

Participants

5

Reactant 3

HCID 6214HexachloroethaneHCID 2733832Lithium HexamethyldisilazideHCID 666965954-Ethyl-5-[4-(trifluoromethyl)phenyl]oxazole

Product 1

HCID 666966452-Chloro-4-ethyl-5-(4-(trifluoromethyl)phenyl)oxazoleYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

LiHMDS (1.0 M in THF, 26 mL, 26 mmol) was added dropwise to a solution of Example 43A (5.75 g, 23.8 mmol) in THF (100 mL) at −78° C. After 30 min solid hexachloroethane (6.21 g, 26.2 mmol) was added in one portion, and the reaction mixture was allowed to proceed for 18 hr with gradual warming to ambient temperature. The reaction was quenched with saturated aq NH4Cl solution (50 mL), and the mixture was partitioned between H2O and Et2O. The aqueous phase was extracted once with Et2O, and the combined organic extract was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified on silica gel (Analogix® Intelliflash 280™; SF40-150 g column; 100% hexane 7 min, then 0% to 20% EtOAc/hexanes eluant, 23 min) which yielded 6.23 g (95%) of the title compound as a pale yellow oil. 1H NMR (300 MHz, DMSO-d6) δ 7.87 (d, J=8.5, 2H), 7.79 (d, J=8.5, 2H), 2.77 (q, J=7.5, 2H), 1.23 (t, J=7.5, 3H). MS (DCI+) m/z 276 (M+H).

Workup

  1. customThe reaction was quenched with saturated aq NH4Cl solution (50 mL)
  2. customthe mixture was partitioned between H2O and Et2O
  3. extractionThe aqueous phase was extracted once with Et2O
  4. extractionthe combined organic extract
  5. washwas washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified on silica gel (Analogix® Intelliflash 280™

Sources & evidence

ORD record
ord-fb614c9790484787bb1f61aae72c916e
Source dataset
uspto-grants-2011_08
Patent number
US07998993B2

Reaction notes

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