(2-bromo-4-fluorophenyl)hydrazine;hydrochloride

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2-Bromo-4-fluorophenyl)hydrazine hydrochloride (1.14 g, 4.72 mmol; Enamine) was suspended in HCl-acetic acid (1.0 M, 25 mL; Aldrich). The product of Example 1A (684 mg, 4.91 mmol) was added and the reaction was heated to 80° C. for 5 hours. The reaction was then allowed to cool and then concentrated. The product was triturated with acetonitrile and isolated by filtration, washing with additional acetonitrile (2×10 mL). The solid was partitioned between 1.0 M NaOH (50 mL) and CHCl3 (3×50 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to give the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 2.05-2.11 (m, 4H), 3.01-3.14 (m, 3H), 3.19-3.26 (m, 2H), 4.17 (s, 2H), 6.96-7.04 (m, 2H); MS (DCI/NH3) m/z 309/311 (M+H)+. Anal. Calcd. for C14H14BrFN2: C, 54.39; H, 4.56; N, 9.06. Found: C, 54.04; H, 4.28; N, 8.90. to cool concentrated The product was triturated with acetonitrile isolated by filtration washing with additional acetonitrile (2×10 mL) The solid was partitioned between 1.0 M NaOH (50 mL) and CHCl3 (3×50 mL) The combined organic extracts were dried over Na2SO4 filtered concentrated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2-Bromo-4-fluorophenyl)hydrazine hydrochloride (1.14 g, 4.72 mmol; Enamine) was suspended in HCl-acetic acid (1.0 M, 25 mL; Aldrich). The product of Example 1A (684 mg, 4.91 mmol) was added and the reaction was heated to 80° C. for 5 hours. The reaction was then allowed to cool and then concentrated. The product was triturated with acetonitrile and isolated by filtration, washing with additional acetonitrile (2×10 mL). The solid was partitioned between 1.0 M NaOH (50 mL) and CHCl3 (3×50 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to give the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 2.05-2.11 (m, 4H), 3.01-3.14 (m, 3H), 3.19-3.26 (m, 2H), 4.17 (s, 2H), 6.96-7.04 (m, 2H); MS (DCI/NH3) m/z 309/311 (M+H)+. Anal. Calcd. for C14H14BrFN2: C, 54.39; H, 4.56; N, 9.06. Found: C, 54.04; H, 4.28; N, 8.90. to cool concentrated The product was triturated with acetonitrile isolated by filtration washing with additional acetonitrile (2×10 mL) The solid was partitioned between 1.0 M NaOH (50 mL) and CHCl3 (3×50 mL) The combined organic extracts were dried over Na2SO4 filtered concentrated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2-Bromo-4-fluorophenyl)hydrazine hydrochloride (1.14 g, 4.72 mmol; Enamine) was suspended in HCl-acetic acid (1.0 M, 25 mL; Aldrich). The product of Example 1A (684 mg, 4.91 mmol) was added and the reaction was heated to 80° C. for 5 hours. The reaction was then allowed to cool and then concentrated. The product was triturated with acetonitrile and isolated by filtration, washing with additional acetonitrile (2×10 mL). The solid was partitioned between 1.0 M NaOH (50 mL) and CHCl3 (3×50 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to give the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 2.05-2.11 (m, 4H), 3.01-3.14 (m, 3H), 3.19-3.26 (m, 2H), 4.17 (s, 2H), 6.96-7.04 (m, 2H); MS (DCI/NH3) m/z 309/311 (M+H)+. Anal. Calcd. for C14H14BrFN2: C, 54.39; H, 4.56; N, 9.06. Found: C, 54.04; H, 4.28; N, 8.90. to cool concentrated The product was triturated with acetonitrile isolated by filtration washing with additional acetonitrile (2×10 mL) The solid was partitioned between 1.0 M NaOH (50 mL) and CHCl3 (3×50 mL) The combined organic extracts were dried over Na2SO4 filtered concentrated

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

Procedure: To a suspension of 7.24 g of (2-bromo-4-fluorophenyl)hydrazine hydrochloric acid salt in 100 mL of acetic acid, 5.5 g of ethyl 2-(2-oxocyclohexyl)-acetate was added. The resulting mixture was heated to reflux for 1 h. Then 10 mL of ethanol was added and the reaction mixture was heated at reflux overnight. The solvent was evaporated and the residue was diluted with EtOAc and washed with saturated aqueous NaHCO3 solution, water, and brine successively. The organic layer was separated and dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was purified by flash chromatography over silica gel (5% EtOAc/hexane) to afford 3.12 g of desired compound. was added The resulting mixture was heated to reflux for 1 h the reaction mixture was heated at reflux overnight The solvent was evaporated the residue was diluted with EtOAc washed with saturated aqueous NaHCO3 solution, water, and brine successively The organic layer was separated dried over anhydrous sodium sulfate filtered evaporated The residue was purified by flash chromatography over silica gel (5% EtOAc/hexane)

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

Procedure: To a suspension of 7.24 g of (2-bromo-4-fluorophenyl)hydrazine hydrochloric acid salt in 100 mL of acetic acid, 5.5 g of ethyl 2-(2-oxocyclohexyl)-acetate was added. The resulting mixture was heated to reflux for 1 h. Then 10 mL of ethanol was added and the reaction mixture was heated at reflux overnight. The solvent was evaporated and the residue was diluted with EtOAc and washed with saturated aqueous NaHCO3 solution, water, and brine successively. The organic layer was separated and dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was purified by flash chromatography over silica gel (5% EtOAc/hexane) to afford 3.12 g of desired compound. was added The resulting mixture was heated to reflux for 1 h the reaction mixture was heated at reflux overnight The solvent was evaporated the residue was diluted with EtOAc washed with saturated aqueous NaHCO3 solution, water, and brine successively The organic layer was separated dried over anhydrous sodium sulfate filtered evaporated The residue was purified by flash chromatography over silica gel (5% EtOAc/hexane)

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

Procedure: To a suspension of 7.24 g of (2-bromo-4-fluorophenyl)hydrazine hydrochloric acid salt in 100 mL of acetic acid, 5.5 g of ethyl 2-(2-oxocyclohexyl)-acetate was added. The resulting mixture was heated to reflux for 1 h. Then 10 mL of ethanol was added and the reaction mixture was heated at reflux overnight. The solvent was evaporated and the residue was diluted with EtOAc and washed with saturated aqueous NaHCO3 solution, water, and brine successively. The organic layer was separated and dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was purified by flash chromatography over silica gel (5% EtOAc/hexane) to afford 3.12 g of desired compound. was added The resulting mixture was heated to reflux for 1 h the reaction mixture was heated at reflux overnight The solvent was evaporated the residue was diluted with EtOAc washed with saturated aqueous NaHCO3 solution, water, and brine successively The organic layer was separated dried over anhydrous sodium sulfate filtered evaporated The residue was purified by flash chromatography over silica gel (5% EtOAc/hexane)

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

Procedure: To a suspension of 7.24 g of (2-bromo-4-fluorophenyl)hydrazine hydrochloric acid salt in 100 mL of acetic acid, 5.5 g of ethyl 2-(2-oxocyclohexyl)-acetate was added. The resulting mixture was heated to reflux for 1 h. Then 10 mL of ethanol was added and the reaction mixture was heated at reflux overnight. The solvent was evaporated and the residue was diluted with EtOAc and washed with saturated aqueous NaHCO3 solution, water, and brine successively. The organic layer was separated and dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was purified by flash chromatography over silica gel (5% EtOAc/hexane) to afford 3.12 g of desired compound. was added The resulting mixture was heated to reflux for 1 h the reaction mixture was heated at reflux overnight The solvent was evaporated the residue was diluted with EtOAc washed with saturated aqueous NaHCO3 solution, water, and brine successively The organic layer was separated dried over anhydrous sodium sulfate filtered evaporated The residue was purified by flash chromatography over silica gel (5% EtOAc/hexane)