4-chloro-2-hydroxybenzonitrile

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: The subtitle compound was prepared according to the method of Example 19 step (b) using the product of step (c) above and 2-hydroxy-4-chlorobenzonitrile.

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

Procedure: The sub-title compound was prepared by the method of Example 1 step (b) using the product of step (b) above and 4-chloro-2-hydroxybenzonitrile.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product from step (b) (1.164 g, 4.06 mmol) was dissolved in anhydrous tetrahydrofuran (80 ml) and 2-hydroxy-4-chlorobenzonitrile (624 mg, 4.06 mmol) and triphenylphosphine (1.172 g, 4.47 mmol) added. The solution was cooled to 0° C. and diethyl azodicarboxylate (0.71 ml, 4.47 mmol) added dropwise. The reaction was allowed to warm to room temperature and stirred for a further 18 h. The reaction was concentrated in vacuo and the residue chromatographed on flash silica, eluting with hexane:ethyl acetate (4:1), to afford the title compound as a colourless oil (1.12 g, 65%). to warm to room temperature The reaction was concentrated in vacuo the residue chromatographed on flash silica eluting with hexane:ethyl acetate (4:1)

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

Procedure: Diethyl azodicarboxylate (1.86 g) was added dropwise to a solution of triphenylphosphine (2.81 g), 4-chloro-2-hydroxybenzonitrile (1.49 g) and the product from step (a) (1.79 g) in tetrahydrofuran (5 ml) and toluene (60 ml) at 0° C. and stirred at 0° C. for 4hand at 20° C. for 18 h. The solvent was removed in vacuo and the residue was purified by chromatography on silica eluting with hexane-diethyl ether (4:1) to give the title compound as a colourless oil (2.80 g). The solvent was removed in vacuo the residue was purified by chromatography on silica eluting with hexane-diethyl ether (4:1)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methanol (100 ml) was added to sodium acetate (1.97 g) and 5-chloro-2-cyanophenol (1.84 g, mp. 155°-157° C.) which was synthesized according to a known method. The mixture was allowed to cool to -78° C., and to the solution was added dropwise a solution of bromine (1.53 g) in methanol (25 ml). After stirring at -78° C. for 30 minutes, the solvent was distilled off under reduced pressure, and ethyl acetate and aqueous potassium bisulfate solution were added to the residue. The ethyl acetate layer was washed with saturated saline solution, dried over anhydrous magnesium sulfate and the solvent was distilled off. The residue was purified by column chromatography on silica gel eluting with ethyl acetate/hexane to obtain 4-bromo-5-chloro-2-cyanophenol (0.53 g, mp. 229°-231° C. (dec.)). was synthesized the solvent was distilled off under reduced pressure, and ethyl acetate and aqueous potassium bisulfate solution were added to the residue The ethyl acetate layer was washed with saturated saline solution dried over anhydrous magnesium sulfate the solvent was distilled off The residue was purified by column chromatography on silica gel eluting with ethyl acetate/hexane

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

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

Procedure: A mixed solution of 5.0 g of 5-chloro-2-cyanophenol and 6.0 g of R-(-)-epichlorohydrin was heated at 120° C. for 2 hours under a nitrogen stream. Toluene (50 ml), 0.1 g of benzyl triethylammonium chloride and 20 ml of a 30% sodium hydroxide were added, and the mixture was stirred at room temperature for 2 hours. The organic layer was separated and dried over magnesium sulfate. The solvent was then evaporated. Ethanol was added to the residue to crystallize it. The crystals were then recrystrallized from ethyl acetate to give 2.4 g (2S)-(+)-(5-chloro-2-cyanophenoxy)-2,3-epoxypropane. The organic layer was separated dried over magnesium sulfate The solvent was then evaporated Ethanol was added to the residue to crystallize it

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

Procedure: A mixed solution of 5.0 g of 5-chloro-2-cyano-phenol and 6.0 g of R-(-)-epichlorohydrin was heated at 120° C. for 2 hours under a nitrogen stream. Toluene (50 ml), 0.1 g of benzyl triethylammonium chloride and 20 ml of a 30% sodium hydroxide were added, and the mixture was stirred at room temperature for 2 hours. The organic layer was separated and dried over magnesium sulfate. The solvent was then evaporated. Ethanol was added to the residue to crystallize it. The crystals were then recrystrallized from ethyl acetate to give 2.4 g (2S)-(+)-(5-chloro-2-cyanophenoxy)-2,3-epoxypropane. The organic layer was separated dried over magnesium sulfate The solvent was then evaporated Ethanol was added to the residue to crystallize it

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

Procedure: The subtitle compound was prepared according to the method of Example 19 step (b) using the product of step (c) above and 2-hydroxy-4-chlorobenzonitrile.

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

Procedure: The subtitle compound was prepared according to the method of Example 19 step (b) using the product of step (c) above and 2-hydroxy-4-chlorobenzonitrile.