4,4,4-trifluoro-3-oxo-2-phenylbutanenitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared according to the procedure described in step 1 of Example 1 from 2-(4-hydrazinophenyl)ethanol hydrochloride and 2-phenyl-2-(trifluoroacetyl)acetonitrile: MS (ESI) m/z 348 [M+H]+, 346 [M−H]−, 1H-NMR (CDCl3) δ 7.58 (2H, J=8.4 Hz), 7.46-7.36 (7H, m), 3.94-3.88 (2H, m), 2.94 (2H, t, J=6.4 Hz).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared according to the procedure described in step 1 of Example 1 from 2-(4-hydrazinophenyl)ethanol hydrochloride and 2-phenyl-2-(trifluoroacetyl)acetonitrile: MS (ESI) m/z 348 [M+H]+, 346 [M−H]−, 1H-NMR (CDCl3) δ 7.58 (2H, J=8.4 Hz), 7.46-7.36 (7H, m), 3.94-3.88 (2H, m), 2.94 (2H, t, J=6.4 Hz).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A crude product was obtained according to the same procedure as described in Example 1 except that α-(trifluoroacetyl)phenylacetonitrile (23.12 g, 0.10 mole) was used. Crude yield: 3.69 g (16.2%). According to the measurement of NMR, it was found that this compound contained 83.2% of the title compound and 11.8% of 3-trifluoromethyl-4-phenyl-5-aminoisoxazole. The crude product was purified by column chromatography on silica gel as described in Example 1 to give the title compound (3.06 g, 13.4%) as colorless crystals, m.p. 91.5°-92.0° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A crude product was obtained according to the same procedure as described in Example 1 except that α-(trifluoroacetyl)phenylacetonitrile (23.12 g, 0.10 mole) was used. Crude yield: 3.69 g (16.2%). According to the measurement of NMR, it was found that this compound contained 83.2% of the title compound and 11.8% of 3-trifluoromethyl-4-phenyl-5-aminoisoxazole. The crude product was purified by column chromatography on silica gel as described in Example 1 to give the title compound (3.06 g, 13.4%) as colorless crystals, m.p. 91.5°-92.0° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methanol (53 ml) and 96% hydroxylamine hydrochloride (2.82 g, 0.0390 mole, 1.3 eq.) were added to -(trifluoroacetyl)phenylacetonitrile (6.96 g, 0.0300 mole) and the mixture was heated under reflux for 68 hours. After methanol was distilled off under reduced pressure and the resulting residue was neutralized with a 8% solution of sodium bicarbonate, the solution was extracted with methylene chloride. After being dried with anhydrous sodium sulfate, it was concentrated and purified by column chromatography on silica gel to give the title compound (5.62 g, 82.1%). The product was recrystallized from benzene-cyclohexane to recover the title compound (4.80 g, 70.1%) as pale yellow needles, m.p. 89°-91° C. the mixture was heated under reflux for 68 hours After methanol was distilled off under reduced pressure the solution was extracted with methylene chloride After being dried with anhydrous sodium sulfate, it was concentrated purified by column chromatography on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared according to the procedure described in step 1 of Example 1 from 2-(4-hydrazinophenyl)ethanol hydrochloride and 2-phenyl-2-(trifluoroacetyl)acetonitrile: MS (ESI) m/z 348 [M+H]+, 346 [M−H]−, 1H-NMR (CDCl3) δ 7.58 (2H, J=8.4 Hz), 7.46-7.36 (7H, m), 3.94-3.88 (2H, m), 2.94 (2H, t, J=6.4 Hz).