3-FLUORO-4-METHYLBENZYL ALCOHOL

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (3-fluoro-4-methylphenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.28 (3H, s), 5.19 (2H, s), 5.72 (1H, d, J=2.0 Hz), 7.18-7.20 (1H, m), 7.07-7.11 (2H, m), 7.41 (1H, dd, J=1.2, 4.8 Hz), 7.56 (1H, d, J=1.6 Hz), 8.03 (1H, s), 8.71 (1H, d, J=4.8 Hz). [M+H] Calc'd for C17H13FN4O, 309; Found, 309.

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

Procedure: The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (3-fluoro-4-methylphenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.28 (3H, s), 5.19 (2H, s), 5.72 (1H, d, J=2.0 Hz), 7.18-7.20 (1H, m), 7.07-7.11 (2H, m), 7.41 (1H, dd, J=1.2, 4.8 Hz), 7.56 (1H, d, J=1.6 Hz), 8.03 (1H, s), 8.71 (1H, d, J=4.8 Hz). [M+H] Calc'd for C17H13FN4O, 309; Found, 309.

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

Procedure: The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (3-fluoro-4-methylphenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.28 (3H, s), 5.19 (2H, s), 5.72 (1H, d, J=2.0 Hz), 7.18-7.20 (1H, m), 7.07-7.11 (2H, m), 7.41 (1H, dd, J=1.2, 4.8 Hz), 7.56 (1H, d, J=1.6 Hz), 8.03 (1H, s), 8.71 (1H, d, J=4.8 Hz). [M+H] Calc'd for C17H13FN4O, 309. Found, 309.

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

Procedure: The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (3-fluoro-4-methylphenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.28 (3H, s), 5.19 (2H, s), 5.72 (1H, d, J=2.0 Hz), 7.18-7.20 (1H, m), 7.07-7.11 (2H, m), 7.41 (1H, dd, J=1.2, 4.8 Hz), 7.56 (1H, d, J=1.6 Hz), 8.03 (1H, s), 8.71 (1H, d, J=4.8 Hz). [M+H] Calc'd for C17H13FN4O, 309. Found, 309.

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Thionyl chloride (0.892 g, 7.5 mmol) was added to a solution of the product of STEP 1 (1.0 g, 6.4 mmol) dropwise at 0° C. After 30 min, the reaction was quenched with crushed ice carefully, and diluted with H2O. The product was extracted with ether. The organic layer washed with saturated NaHCO3, brine and dried with Na0.2SO4. Ether was evaporated and the residue was purified by chromatography (on silica gel, ethyl acetate/hexane=1/9) to give a clear liquid in 10.5 g. NMR spectra of the product were consistent for the proposed structure. the reaction was quenched with crushed ice carefully diluted with H2O The product was extracted with ether The organic layer washed with saturated NaHCO3, brine dried with Na0.2SO4 Ether was evaporated the residue was purified by chromatography (on silica gel, ethyl acetate/hexane=1/9) to give a clear liquid in 10.5 g

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

Procedure: 3-fluoro-p-anisaldehyde (12.5 g, 81.1 mmol) was dissolved in 100 ml THF. Under N2 a solution of diisobutylalumium hydride (100 ml, 1M in THF) was added at 0° C. over 30 min. The reaction was stirred for 30 min and quenched with 250 ml 1 N HCl solution. The mixture was stirred for 15 min and filtered through a short column of Celite®. The aqueous layer was extracted with ethyl acetate. The combined organic layer was dried with MgSO4, and concentrated to give an oil in 11.6 g. This product was used without further purification. NMR spectra of the product were consistent for the proposed structure. quenched with 250 ml 1 N HCl solution The mixture was stirred for 15 min filtered through a short column of Celite® The aqueous layer was extracted with ethyl acetate The combined organic layer was dried with MgSO4 concentrated to give an oil in 11.6 g This product was used without further purification

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

Procedure: Thionyl chloride (0.892 g, 7.5 mmol) was added to a solution of the product of STEP 1 (1.0 g, 6.4 mmol) in 10 ml ether dropwise at 0° C. After 30 min, the reaction was quenched with crushed ice carefully, and diluted with H2O. The product was extracted with ether. The organic layer was washed with saturated NaHCO3 solution, brine, dried with Na2SO4, and concentrated. The residue was purified by chromatography (on silica gel, ethyl acetate/hexane=1/9) to give a colorless liquid in 10.5 g. NMR spectra of the product were consistent for the proposed structure. the reaction was quenched with crushed ice carefully diluted with H2O The product was extracted with ether The organic layer was washed with saturated NaHCO3 solution, brine dried with Na2SO4 concentrated The residue was purified by chromatography (on silica gel, ethyl acetate/hexane=1/9) to give a colorless liquid in 10.5 g

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

Procedure: 3-fluoro-p-anisaldehyde (12.5 g, 81.1 mmol) was dissolved in 100 ml THF. Under N2 a solution of diisobutylalumium hydride (100 ml, 1M in THF) was added at 0° C. over 30 min. The reaction was stirred for 30 min and quenched with 250 ml 1N HCl solution. The resulting mixture was stirred for 15 min and filtered through a short column of Celite®. The product was extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was dried with MgSO4, and concentrated to give a viscous oil in 11.6 g. This product was used without further purification. NMR spectra of the product were consistent for the proposed structure. quenched with 250 ml 1N HCl solution The resulting mixture was stirred for 15 min filtered through a short column of Celite® The product was extracted with ethyl acetate The aqueous layer was extracted with ethyl acetate The combined organic layer was dried with MgSO4 concentrated to give a viscous oil in 11.6 g This product was used without further purification

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

Procedure: The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (3-fluoro-4-methylphenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.28 (3H, s), 5.19 (2H, s), 5.72 (1H, d, J=2.0 Hz), 7.18-7.20 (1H, m), 7.07-7.11 (2H, m), 7.41 (1H, dd, J=1.2, 4.8 Hz), 7.56 (1H, d, J=1.6 Hz), 8.03 (1H, s), 8.71 (1H, d, J=4.8 Hz). [M+H] Calc'd for C17H13FN4O, 309; Found, 309.

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

Procedure: The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (3-fluoro-4-methylphenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.28 (3H, s), 5.19 (2H, s), 5.72 (1H, d, J=2.0 Hz), 7.18-7.20 (1H, m), 7.07-7.11 (2H, m), 7.41 (1H, dd, J=1.2, 4.8 Hz), 7.56 (1H, d, J=1.6 Hz), 8.03 (1H, s), 8.71 (1H, d, J=4.8 Hz). [M+H] Calc'd for C17H13FN4O, 309. Found, 309.