1,3-dichloro-2-(methoxymethoxy)propane

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

Procedure: Potassium hydroxide (2.57 g) was dissolved in dimethyl sulfoxide (8.0 mL). (4-Chlorophenyl)acetonitrile (1.58 g, 10.4 mmol) and 1,3-dichloro-2-(methoxymethoxy)propane (1.993 g) were dissolved in ethyl ether (3 mL), and this mixture was added dropwise to the vigorously stirred potassium hydroxide solution at room temperature. After stirring at room temperature for one hour, the reaction was quenched by adding ice-cold water (5.5 mL). The mixture was filtered through a pad of celite which was washed with ether (30 mL). The filtrate was added to a separatory funnel, and the aqueous layer was extracted with ether (3×15 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated. The product was purified by silica gel chromatography to provide 1-(4-chlorophenyl)-3-(methoxymethoxy)cyclobutanecarbonitrile (1.28 g) as a mixture of isomers (ca. 2:1). the reaction was quenched by adding ice-cold water (5.5 mL) The mixture was filtered through a pad of celite which was washed with ether (30 mL) The filtrate was added to a separatory funnel the aqueous layer was extracted with ether (3×15 mL) dried over magnesium sulfate filtered concentrated The product was purified by silica gel chromatography

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

Procedure: Potassium hydroxide (2.57 g) was dissolved in dimethyl sulfoxide (8.0 mL). (4-Chlorophenyl)acetonitrile (1.58 g, 10.4 mmol) and 1,3-dichloro-2-(methoxymethoxy)propane (1.993 g) were dissolved in ethyl ether (3 mL), and this mixture was added dropwise to the vigorously stirred potassium hydroxide solution at room temperature. After stirring at room temperature for one hour, the reaction was quenched by adding ice-cold water (5.5 mL). The mixture was filtered through a pad of celite which was washed with ether (30 mL). The filtrate was added to a separatory funnel, and the aqueous layer was extracted with ether (3×15 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated. The product was purified by silica gel chromatography to provide 1-(4-chlorophenyl)-3-(methoxymethoxy)cyclobutanecarbonitrile (1.28 g) as a mixture of isomers (ca. 2:1). the reaction was quenched by adding ice-cold water (5.5 mL) The mixture was filtered through a pad of celite which was washed with ether (30 mL) The filtrate was added to a separatory funnel the aqueous layer was extracted with ether (3×15 mL) dried over magnesium sulfate filtered concentrated The product was purified by silica gel chromatography

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

Procedure: 1,3-Dichloro-2-propanol (10.0 g, 77.5 mmol) was dissolved in dimethoxymethane (150 ml), lithium bromide (20.2 g, 232.5 mmol) and p-toluenesulfonic acid (1.33 g, 7.8 mmol) were added, and the mixture was stirred at room temperature for 3 days. After completion of the reaction, the reaction mixture was neutralized and partitioned with 5% aqueous sodium hydrogencarbonate solution (50 ml) and dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was filtered off and the filtrate was concentrated to give a crude title compound (12.44 g). The crude title compound was distilled under reduced pressure (15 mmHg, 83° C.) to give a pure title compound (7.7 g, yield 57.5%). After completion of the reaction partitioned with 5% aqueous sodium hydrogencarbonate solution (50 ml) dried over anhydrous magnesium sulfate Anhydrous magnesium sulfate was filtered off the filtrate was concentrated to give a crude title compound (12.44 g) The crude title compound was distilled under reduced pressure (15 mmHg, 83° C.)

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

Procedure: Potassium hydroxide (2.57 g) was dissolved in dimethyl sulfoxide (8.0 mL). (4-Chlorophenyl)acetonitrile (1.58 g, 10.4 mmol) and 1,3-dichloro-2-(methoxymethoxy)propane (1.993 g) were dissolved in ethyl ether (3 mL), and this mixture was added dropwise to the vigorously stirred potassium hydroxide solution at room temperature. After stirring at room temperature for one hour, the reaction was quenched by adding ice-cold water (5.5 mL). The mixture was filtered through a pad of celite which was washed with ether (30 mL). The filtrate was added to a separatory funnel, and the aqueous layer was extracted with ether (3×15 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated. The product was purified by silica gel chromatography to provide 1-(4-chlorophenyl)-3-(methoxymethoxy)cyclobutanecarbonitrile (1.28 g) as a mixture of isomers (ca. 2:1). the reaction was quenched by adding ice-cold water (5.5 mL) The mixture was filtered through a pad of celite which was washed with ether (30 mL) The filtrate was added to a separatory funnel the aqueous layer was extracted with ether (3×15 mL) dried over magnesium sulfate filtered concentrated The product was purified by silica gel chromatography

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

Procedure: Potassium hydroxide (2.57 g) was dissolved in dimethyl sulfoxide (8.0 mL). (4-Chlorophenyl)acetonitrile (1.58 g, 10.4 mmol) and 1,3-dichloro-2-(methoxymethoxy)propane (1.993 g) were dissolved in ethyl ether (3 mL), and this mixture was added dropwise to the vigorously stirred potassium hydroxide solution at room temperature. After stirring at room temperature for one hour, the reaction was quenched by adding ice-cold water (5.5 mL). The mixture was filtered through a pad of celite which was washed with ether (30 mL). The filtrate was added to a separatory funnel, and the aqueous layer was extracted with ether (3×15 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated. The product was purified by silica gel chromatography to provide 1-(4-chlorophenyl)-3-(methoxymethoxy)cyclobutanecarbonitrile (1.28 g) as a mixture of isomers (ca. 2:1). the reaction was quenched by adding ice-cold water (5.5 mL) The mixture was filtered through a pad of celite which was washed with ether (30 mL) The filtrate was added to a separatory funnel the aqueous layer was extracted with ether (3×15 mL) dried over magnesium sulfate filtered concentrated The product was purified by silica gel chromatography