(2,3,4-trifluorophenyl)hydrazine

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

Procedure: To a mixed solvent of 1N hydrochloric acid aqueous solution (120 ml) and ethanol (120 ml), were added 2,3,4-trifluorophenylhydrazine (9.3 g) and ethyl 2-(ethoxymethylene)acetoacetate (10.7 g) prepared according to a method described in J. Chem. Soc. Perkin trans. I, 1875 (1988), and the mixture was stirred at reflux temperature for three hours. Next, sodium hydroxide (2.8 g) was added and the mixture was further stirred for an hour. Ethanol was evaporated in vacuo, the organic layer was separated with toluene, hydrochloric acid was added to the aqueous layer and the precipitated solid was collected by filtration to give the titled compound (10 g). prepared at reflux temperature for three hours the mixture was further stirred for an hour Ethanol was evaporated in vacuo the organic layer was separated with toluene, hydrochloric acid was added to the aqueous layer the precipitated solid was collected by filtration

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

Procedure: 2,3,4-Trifluoroaniline (25 g) was added to concentrated hydrochloric acid (125 ml), and an aqueous solution (20 ml) of sodium nitrite (12.9 g) was added dropwise under ice-cooling. A solution of tin (II) chloride (114.6 g) in concentrated hydrochloric acid (50 ml) was separately prepared and it was added dropwise to the reaction solution. The precipitated solid was collected by filtration, added to an aqueous solution of sodium hydroxide and the aqueous solution was extracted with toluene to give 2,3,4-trifluorophenylhydrazine (9.3 g). cooling it was added dropwise to the reaction solution The precipitated solid was collected by filtration added to an aqueous solution of sodium hydroxide the aqueous solution was extracted with toluene

Conditions: temp:185.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a dry 15 mL ChemGlass pressure bottle under N2 was added (2,3,4-trifluorophenyl)hydrazine (359 mg, 2.212 mmol), 4-iodo-2-fluoro-3-formylpyridine (555.1 mg, 2.212 mmol), and anhydrous NMP (5 mL). The reaction mixture was flushed with argon, securely capped, and heated at 185° C. for 3 h. The reaction mixture was worked up according to the procedure described in Intermediate 69A. The product was purified by Biotage Silica gel chromatography using a 25 g Thompson Single Step™ silica cartridge with a linear gradient from 100% hexanes to 100% CH2Cl2 over 12 column volumes gave 162.9 mg (20.4%) of the title compound as a yellow solid. LC/MS (Condition B): ret. T=4.0 min, (M+H)+ 375.93. The reaction mixture was flushed with argon securely capped The product was purified by Biotage Silica gel chromatography