Phosphorus oxychloride → 2-(4-Trifluoromethylphenyl)-4-chloromethyl-5-methyloxazole

HRID 1993032Notes

Reaction equation

HRID 1993032 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH3:6][C:7]1[N+:8]([O-])=[C:9]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[O:10][C:11]=1[CH3:12]>ClCCl>[Cl:3][CH2:6][C:7]1[N:8]=[C:9]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[O:10][C:11]=1[CH3:12]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 10515280Oxazole, 4,5-dimethyl-2-[4-(trifluoromethyl)phenyl]-, 3-oxide

Product 1

HCID 102363332-(4-Trifluoromethylphenyl)-4-chloromethyl-5-methyloxazoleYield 15%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Phosphorous oxychloride (0.72 mL, 7.8 mmol) was added dropwise to an oven-dried 100 mL pear-shaped flask charged with 18.1 (1.8 g, 7.00 mmol) and dichloromethane (20 mL). The reaction was refluxed under nitrogen atmosphere for 30 minutes and then cooled to room temperature. The reaction was washed with water (2×250 mL) and the combined aqueous layers were back extracted with DCM (2×25 mL). The combined organic layers were washed with brine and dried (Na2SO4). The solvent was removed under reduced pressure and the resulting residue was purified via radial chromatography (15% diethyl ether in hexanes) to yield 216 mg (15%) of 4-chloromethyl-5-methyl-2-(4-trifluoromethyl-phenyl)-oxazole as a white solid. LC/MSD m/e: 276.0 (M+H); 1H NMR (400 MHz) (CDCl3) δ 8.15 (2H, d, J=8.0 Hz), 7.73 (2H. d, J=8.0 Hz), 4.59 (2H, s), 2.48 (2H, s).

Workup

  1. temperatureThe reaction was refluxed under nitrogen atmosphere for 30 minutes
  2. washThe reaction was washed with water (2×250 mL)
  3. extractionthe combined aqueous layers were back extracted with DCM (2×25 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. customThe solvent was removed under reduced pressure
  7. customthe resulting residue was purified via radial chromatography (15% diethyl ether in hexanes)

Sources & evidence

ORD record
ord-4dfc18631b1a46e783a01d1bfe906dae
Source dataset
uspto-grants-2010_01
Patent number
US07649110B2

Reaction notes

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