Hexachloroethane → 2-Chloro-5-(4-(difluoromethyl)phenyl)-4-methyloxazole

HRID 1672570Notes

Reaction equation

HRID 1672570 reaction equation
[F:1][CH:2]([F:15])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][CH:12]=[N:11][C:10]=2[CH3:14])=[CH:5][CH:4]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:26]C(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[Cl:26][C:12]1[O:13][C:9]([C:6]2[CH:5]=[CH:4][C:3]([CH:2]([F:1])[F:15])=[CH:8][CH:7]=2)=[C:10]([CH3:14])[N:11]=1

Participants

5

Reactant 3

HCID 6214HexachloroethaneHCID 2733832Lithium HexamethyldisilazideHCID 666966055-(4-(Difluoromethyl)phenyl)-4-methyloxazole

Product 1

HCID 666966302-Chloro-5-(4-(difluoromethyl)phenyl)-4-methyloxazoleYield 76.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Example 38D (4.39 g, 21.0 mmol) in THF (100 mL) at −78° C. was added LiHMDS (1.0 M in THF, 23 ml, 23 mmol) slowly via syringe. The solution was stirred 45 min, and then solid hexachloroethane (5.46 g, 23.1 mmol) was added in one portion. The reaction was allowed to proceed for 24 hr, gradually warming to ambient temperature. The reaction was quenched with half-saturated aq NH4Cl solution, and the product was extracted with Et2O. The combined organic extract was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Flash chromatography (Analogix® Intelliflash 280™; 0% to 20% EtOAc/hexanes eluant; SF40-240 g column) yielded 3.91 g (76%) of the title compound as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 7.72 (m, 4H), 7.10 (t, J=55.7, 1H), 2.39 (s, 3H). MS (DCI+) m/z 244 (M+H).

Workup

  1. waitto proceed for 24 hr
  2. customThe reaction was quenched with half-saturated aq NH4Cl solution
  3. extractionthe product was extracted with Et2O
  4. extractionThe combined organic extract
  5. washwas washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8873bee5cd0f4085b29a85c06ce01cbb
Source dataset
uspto-grants-2011_08
Patent number
US07998993B2

Reaction notes

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