(2-chloro-6-methylphenyl)methanol

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

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

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

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

Procedure: A solution of (2-chloro-6-methylphenyl)methanol (Step A, 3 g, 19.1 mmol) and diisopropyl azodicarboxylate (DIAD, 4.13 ml, 21 mmol) in THF (20 ml) was added drop wise to a solution of ethyl 2-(3-hydroxyphenyl)acetate (3.79 g, 21 mmol) and triphenylphosphine (5.48 g, 21 mmol) in THF (30 ml) at 0° C. under argon. The reaction mixture was stirred at the same temperature for 4 hours, diluted with ether and washed with water. The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1) to give the title compound. washed with water The organic layer was dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1)

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

Procedure: To a stirred solution of 2-chloro-6-methylbenzaldehyde (6.11 g, 39.5 mmol) in THF(2): methanol(3) (30 ml) was added in portion NaBH4 (2.24 g, 59.28 mmol) at 0° C. under argon. The reaction mixture was stirred at the same temperature for 1.3 hours and then quenched with cold sat. NH4Cl solution, extracted with EtOAc, dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1) to give the title compound. quenched with cold sat. NH4Cl solution extracted with EtOAc dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1)

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

Procedure: To a stirred solution of 2-chloro-6-methylbenzaldehyde (6.11 g, 39.5 mmol) in THF(2): methanol(3) (30 ml) was added in portion NaBH4 (2.24 g, 59.28 mmol) at 0° C. under argon. The reaction mixture was stirred at the same temperature for 1.3 hours and then quenched with cold sat. NH4Cl solution, extracted with EtOAc, dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1) to give the title compound. quenched with cold sat. NH4Cl solution extracted with EtOAc dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1)

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

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

Procedure: The 2-chloro-6-methylbenzyl alcohol is dissolved in 100 ml of benzene, treated with 25 ml of thionyl chloride and the mixture is heated at reflux for 3 hours. Concentration of this mixture to dryness leaves a liquid which partly solidifies. The product containing liquid is decanted from the solid by-product and distilled to yield 7.8 g of alpha,2-dichloro-6-methyltoluene as a colorless liquid with bp. 118°-122° C./17-18 mm of Hg. the mixture is heated at reflux for 3 hours Concentration of this mixture to dryness leaves a liquid which The product containing liquid is decanted from the solid by-product distilled

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

Procedure: A solution of 24 g of 2-chloro-6-methylbenzaldehyde [L. G. Humber, J. Med. Chem., 7, 826 (1964)] in 200 ml of methanol is cooled in an ice bath while 6.0 g of sodium borohydride is added in portions. After stirring overnight at room temperature, the mixture is concentrated to dryness and the residue is partitioned between water and ether. The organic layer is washed with dilute hydrochloric acid, dried, and concentrated to yield the crude product. Recrystallization from benzene/hexane gives 20.8 g of 2-chloro-6-methylbenzyl alcohol, mp 83°-86° C. in two crops. is added in portions the mixture is concentrated to dryness the residue is partitioned between water and ether The organic layer is washed with dilute hydrochloric acid dried concentrated to yield the crude product Recrystallization from benzene/hexane

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

Procedure: Under ice cooling, 5 drops of dimethylformamide and 0.75 ml of thionyl chloride were added to a solution of 1.24 g of 2-chloro-6-methylbenzyl alcohol in 15 ml of toluene. The mixture was stirred at ambient temperature for 2 hours. The reaction mixture was concentrated under reduced pressure and the residue was then azeotropically distilled with 5 ml of toluene 3 times to give an oil. The resulting oil was dissolved in 15 ml of acetonitrile, and 2.08 g of triphenylphosphine was added to the solution. The mixture was heated under reflux for 16 hours. The reaction mixture was concentrated under reduced pressure and the collected crystals were washed with ethyl acetate to give 3.15 g of (2-chloro-6-methylbenzyl)(triphenyl)phosphonium chloride as colorless crystals. The reaction mixture was concentrated under reduced pressure the residue was then azeotropically distilled with 5 ml of toluene 3 times to give an oil The mixture was heated under reflux for 16 hours The reaction mixture was concentrated under reduced pressure the collected crystals were washed with ethyl acetate

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

Procedure: Under ice cooling, 185 mg of sodium borohydride was added to a solution of 1.51 g of 2-chloro-6-methylbenzaldehyde in 15 ml of methanol, followed by stirring for 35 minutes. The reaction mixture was concentrated under reduced pressure and saturated aqueous ammonium chloride was added to the residue. The mixture was extracted with diethyl ether. The organic layer was washed with saturated aqueous sodium chloride and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give 1.24 g of 2-chloro-6-methylbenzyl alcohol as colorless crystals. The reaction mixture was concentrated under reduced pressure and saturated aqueous ammonium chloride was added to the residue The mixture was extracted with diethyl ether The organic layer was washed with saturated aqueous sodium chloride dried over anhydrous sodium sulfate After filtration the filtrate was concentrated the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate)

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

Procedure: A solution of (2-chloro-6-methylphenyl)methanol (Step A, 3 g, 19.1 mmol) and diisopropyl azodicarboxylate (DIAD, 4.13 ml, 21 mmol) in THF (20 ml) was added drop wise to a solution of ethyl 2-(3-hydroxyphenyl)acetate (3.79 g, 21 mmol) and triphenylphosphine (5.48 g, 21 mmol) in THF (30 ml) at 0° C. under argon. The reaction mixture was stirred at the same temperature for 4 hours, diluted with ether and washed with water. The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1) to give the title compound. washed with water The organic layer was dried over Na2SO4 filtered concentrated purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1)