2-Amino-4-(trifluoromethyl)phenol → 2-ChloroMethyl-5-trifluoroMethyl-benzooxazole

HRID 1772284Notes

Reaction equation

[Cl:1][CH2:2][C:3]([O:10][CH2:11][CH3:12])(OCC)OCC.[NH2:13][C:14]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=CC=1O>C(O)(=O)C>[Cl:1][CH2:2][C:3]1[O:10][C:11]2[CH:12]=[CH:17][C:18]([C:20]([F:23])([F:22])[F:21])=[CH:19][C:14]=2[N:13]=1

Participants

Conditions

Temperature: 120 °C

Procedure

2-Chloro-1,1,1-triethoxyethane (410 μL, 2.15 mmol) was added to a suspension of 2-amino-4-trifluoromethylphenol (370 mg, 1.79 mmol) in acetic acid (7 mL); during the addition the solution began to clear. The solution was heated at 120° C. (external temperature). After three hours the reaction mixture was cooled and the volatiles were removed under reduced pressure. Purification by silica gel chromatography, eluting with a gradient of 0 to 10% ethyl acetate in heptanes, gave 2-chloromethyl-5-trifluoromethyl-benzoxazole as a yellow oil (324 mg, 77%). (CI, m/z): [M+H]+ 236; 1H NMR (CDCl3): δ 8.05 (s, 1H), 7.66-7.73 (m, 2H), 4.79 (s, 2H); 19F NMR (376 MHz, CDCl3): δ ppm −61.26 (s, 3F).

Workup

additionduring the addition the solution
temperatureAfter three hours the reaction mixture was cooled
customthe volatiles were removed under reduced pressure
customPurification by silica gel chromatography
washeluting with a gradient of 0 to 10% ethyl acetate in heptanes

Sources & evidence

ORD record: ord-461639f1df16415685603abe2b8a8c9c
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249102B2

Reaction notes

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