(2-bromo-3-methylphenyl)methanol

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

Procedure: To a solution of (2-bromo-3-methylphenyl)methanol (0.5 g, 2.49 mmol), triphenylphosphine (1.31 g, 4.97 mmol) and 2-chloro-5-(trifluoromethyl)phenol (0.37 mL, 2.74 mmol) in DCM (12.4 mL) at 0° C. was added diethyl azodicarboxylate (1.97 mL, 4.97 mmol) and the reaction warmed to RT for 30 min. The reaction was quenched with water and the aqueous layer was extracted with EtOAc. The organic layer was then washed with water and brine (3× ea.), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography (0-50% Hexene/EtOAc) to afford 2-bromo-1-((2-chloro-5-(trifluoromethyl)phenoxy)methyl)-3-methylbenzene as a clear oil. The reaction was quenched with water the aqueous layer was extracted with EtOAc The organic layer was then washed with water and brine (3× ea.) dried over Na2SO4 concentrated in vacuo The crude material was purified by column chromatography (0-50% Hexene/EtOAc)

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

Procedure: To a solution of (2-bromo-3-methylphenyl)methanol (0.5 g, 2.49 mmol), triphenylphosphine (1.31 g, 4.97 mmol) and 2-chloro-5-(trifluoromethyl)phenol (0.37 mL, 2.74 mmol) in DCM (12.4 mL) at 0° C. was added diethyl azodicarboxylate (1.97 mL, 4.97 mmol) and the reaction warmed to RT for 30 min. The reaction was quenched with water and the aqueous layer was extracted with EtOAc. The organic layer was then washed with water and brine (3× ea.), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography (0-50% Hexene/EtOAc) to afford 2-bromo-1-((2-chloro-5-(trifluoromethyl)phenoxy)methyl)-3-methylbenzene as a clear oil. The reaction was quenched with water the aqueous layer was extracted with EtOAc The organic layer was then washed with water and brine (3× ea.) dried over Na2SO4 concentrated in vacuo The crude material was purified by column chromatography (0-50% Hexene/EtOAc)

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

Procedure: A solution of 2-bromo-3-methylbenzoic acid (4.0 g, 18.60 mmol) in THF (93 mL) was cooled to 0° C. and LAH (1.41 g, 37.2 mmol) added by portion. After the reaction completed, aq. K/Na tartrate was added and the reaction stirred overnight. The aqueous layer was extracted with EtOAc and the organic layer was then washed with water and brine (3× ea.), dried over Na2SO4 and concentrated in vacuo to give (2-bromo-3-methylphenyl)methanol as a clear oil that was used without further purification. The aqueous layer was extracted with EtOAc the organic layer was then washed with water and brine (3× ea.) dried over Na2SO4 concentrated in vacuo

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 12.49 g (0. 0621 mol) of o-bromo-m-methylbenzyl alcohol in 400 ml of ether cooled to -20° C. was added in portions 13.3 ml (0.1335 mol) of n-butyllithium (10M) in hexane over a 20 min period, and the reaction mixture was allowed to warm to room temperature and stirred 1 hr. The above reaction mixture was cooled to -20° C., 14.63 g (0.136 mol) of pyridine-2-carboxaldehyde in 50 ml of ether was added to the mixture over an 1 hr period (the mixture turns purple), and the resulting reaction mixture was allowed to warm to room temperature and stirred for 1 hr. Ammonium chloride solution (100 ml) and 200 ml of ethyl acetate were added to the mixture with stirring, and the mixture was extracted with ethyl acetate (2×200 ml). The combined organic layer was washed with brine, dried over sodium sulfate, and concentrated. The diol was was triturated with 100 ml of ether, filtered, and the solid product was washed with hexane (yield: 6.6 g; 46%) to afford 2-[1-hydroxy-(2'-hydroxymethyl-6'-methyl)-benzyl]-pyridine (Formula XIII: R1 =R7 =H; R2 =6'--CH3), as a pale yellow solid, m.p. 129°-132° C. to warm to room temperature The above reaction mixture was cooled to -20° C. the resulting reaction mixture to warm to room temperature stirred for 1 hr with stirring the mixture was extracted with ethyl acetate (2×200 ml) The combined organic layer was washed with brine dried over sodium sulfate concentrated The diol was was triturated with 100 ml of ether filtered the solid product was washed with hexane (yield: 6.6 g; 46%)

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

Procedure: To a solution of (2-bromo-3-methylphenyl)methanol (0.5 g, 2.49 mmol), triphenylphosphine (1.31 g, 4.97 mmol) and 2-chloro-5-(trifluoromethyl)phenol (0.37 mL, 2.74 mmol) in DCM (12.4 mL) at 0° C. was added diethyl azodicarboxylate (1.97 mL, 4.97 mmol) and the reaction warmed to RT for 30 min. The reaction was quenched with water and the aqueous layer was extracted with EtOAc. The organic layer was then washed with water and brine (3× ea.), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography (0-50% Hexene/EtOAc) to afford 2-bromo-1-((2-chloro-5-(trifluoromethyl)phenoxy)methyl)-3-methylbenzene as a clear oil. The reaction was quenched with water the aqueous layer was extracted with EtOAc The organic layer was then washed with water and brine (3× ea.) dried over Na2SO4 concentrated in vacuo The crude material was purified by column chromatography (0-50% Hexene/EtOAc)

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

Procedure: A solution of 2-bromo-3-methylbenzoic acid (4.0 g, 18.60 mmol) in THF (93 mL) was cooled to 0° C. and LAH (1.41 g, 37.2 mmol) added by portion. After the reaction completed, aq. K/Na tartrate was added and the reaction stirred overnight. The aqueous layer was extracted with EtOAc and the organic layer was then washed with water and brine (3× ea.), dried over Na2SO4 and concentrated in vacuo to give (2-bromo-3-methylphenyl)methanol as a clear oil that was used without further purification. The aqueous layer was extracted with EtOAc the organic layer was then washed with water and brine (3× ea.) dried over Na2SO4 concentrated in vacuo