2-(cyclopropylmethoxy)phenol

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

Procedure: Catechol (110 g) is dissolved in 800 ml isopropanol. A solution of sodium hydroxide (41 g) in 45 ml water is added followed by cyclopropylmethyl chloride (155 g, 70% pure) and potassium iodide (5 g). The reaction mixture is stirred under nitrogen at reflux for 16 hours. The mixture is cooled to room temperature and the solid filtered off and washed with isopropanol. The filtrate is concentrated under reduced pressure, the brown residue dissolved in toluene (600 ml), 3 N hydrochloric acid added to acidify to pH 1 and the organic phase washed consecutively with water (4×100 ml), aqueous sodium bisulfite and water (3×100 ml). The organic layer is dried over anhydrous sodium sulfate, filtered through basic alumina (300 g) to remove any remaining catechol and concentrated under reduced pressure. The residue is distilled in vacuo through a Vigreaux column with reflux distilling head to give 2-(cyclopropylmethoxy)phenol, bp. 66°-68°/0.1 mm. at reflux for 16 hours the solid filtered off washed with isopropanol The filtrate is concentrated under reduced pressure the brown residue dissolved in toluene (600 ml) 3 N hydrochloric acid added the organic phase washed consecutively with water (4×100 ml), aqueous sodium bisulfite and water (3×100 ml) The organic layer is dried over anhydrous sodium sulfate filtered through basic alumina (300 g) to remove any remaining catechol concentrated under reduced pressure The residue is distilled in vacuo through a Vigreaux column with reflux distilling head

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

Procedure: Catechol (110 g) is dissolved in 800 ml isopropanol. A solution of sodium hydroxide (41 g) in 45 ml water is added followed by cyclopropylmethyl chloride (155 g, 70% pure) and potassium iodide (5 g). The reaction mixture is stirred under nitrogen at reflux for 16 hours. The mixture is cooled to room temperature and the solid filtered off and washed with isopropanol. The filtrate is concentrated under reduced pressure, the brown residue dissolved in toluene (600 ml), 3 N hydrochloric acid added to acidify to pH 1 and the organic phase washed consecutively with water (4×100 ml), aqueous sodium bisulfite and water (3×100 ml). The organic layer is dried over anhydrous sodium sulfate, filtered through basic alumina (300 g) to remove any remaining catechol and concentrated under reduced pressure. The residue is distilled in vacuo through a Vigreaux column with reflux distilling head to give 2-(cyclopropylmethoxy)phenol, bp. 66°-68°/0.1 mm. at reflux for 16 hours the solid filtered off washed with isopropanol The filtrate is concentrated under reduced pressure the brown residue dissolved in toluene (600 ml) 3 N hydrochloric acid added the organic phase washed consecutively with water (4×100 ml), aqueous sodium bisulfite and water (3×100 ml) The organic layer is dried over anhydrous sodium sulfate filtered through basic alumina (300 g) to remove any remaining catechol concentrated under reduced pressure The residue is distilled in vacuo through a Vigreaux column with reflux distilling head

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

Procedure: A mixture of (S)-benzyl 2,3-epoxypropyl ether (8.95 g as described in Heterocycles Vol. 16, 381, 1981), o-cyclopropylmethoxyphenol (8.95 g) in 36 ml acetone and 4 ml hexane, to which is added powdered potassium carbonate (6.9 g), is stirred at reflux in nitrogen atmosphere for 74 hours. After cooling to room temperature the solid is filtered off and washed with acetone. The filtrate is concentrated under reduced pressure, the residue is dissolved in ether, the ether solution is washed 2x with water and dried over anhydrous sodium sulfate, filtered, and the filtrate is evaporated to dryness. The crude oil is distilled in vacuo, at 199°-212°/0.2 mm to yield (S)-1-benzyloxy-3-[o-(cyclopropylmethoxy)phenoxy]-2-hydroxypropane. at reflux in nitrogen atmosphere for 74 hours is filtered off washed with acetone The filtrate is concentrated under reduced pressure the residue is dissolved in ether the ether solution is washed 2x with water dried over anhydrous sodium sulfate filtered the filtrate is evaporated to dryness The crude oil is distilled in vacuo, at 199°-212°/0.2 mm

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

Procedure: A mixture of (S)-benzyl 2,3-epoxypropyl ether (8.95 g as described in Heterocycles Vol. 16, 381, 1981), o-cyclopropylmethoxyphenol (8.95 g) in 36 ml acetone and 4 ml hexane, to which is added powdered potassium carbonate (6.9 g), is stirred at reflux in nitrogen atmosphere for 74 hours. After cooling to room temperature the solid is filtered off and washed with acetone. The filtrate is concentrated under reduced pressure, the residue is dissolved in ether, the ether solution is washed 2x with water and dried over anhydrous sodium sulfate, filtered, and the filtrate is evaporated to dryness. The crude oil is distilled in vacuo, at 199°-212°/0.2 mm to yield (S)-1-benzyloxy-3-[o-(cyclopropylmethoxy)phenoxy]-2-hydroxypropane. at reflux in nitrogen atmosphere for 74 hours is filtered off washed with acetone The filtrate is concentrated under reduced pressure the residue is dissolved in ether the ether solution is washed 2x with water dried over anhydrous sodium sulfate filtered the filtrate is evaporated to dryness The crude oil is distilled in vacuo, at 199°-212°/0.2 mm

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

Procedure: Catechol (110 g) is dissolved in 800 ml isopropanol. A solution of sodium hydroxide (41 g) in 45 ml water is added followed by cyclopropylmethyl chloride (155 g, 70% pure) and potassium iodide (5 g). The reaction mixture is stirred under nitrogen at reflux for 16 hours. The mixture is cooled to room temperature and the solid filtered off and washed with isopropanol. The filtrate is concentrated under reduced pressure, the brown residue dissolved in toluene (600 ml), 3 N hydrochloric acid added to acidify to pH 1 and the organic phase washed consecutively with water (4×100 ml), aqueous sodium bisulfite and water (3×100 ml). The organic layer is dried over anhydrous sodium sulfate, filtered through basic alumina (300 g) to remove any remaining catechol and concentrated under reduced pressure. The residue is distilled in vacuo through a Vigreaux column with reflux distilling head to give 2-(cyclopropylmethoxy)phenol, bp. 66°-68°/0.1 mm. at reflux for 16 hours the solid filtered off washed with isopropanol The filtrate is concentrated under reduced pressure the brown residue dissolved in toluene (600 ml) 3 N hydrochloric acid added the organic phase washed consecutively with water (4×100 ml), aqueous sodium bisulfite and water (3×100 ml) The organic layer is dried over anhydrous sodium sulfate filtered through basic alumina (300 g) to remove any remaining catechol concentrated under reduced pressure The residue is distilled in vacuo through a Vigreaux column with reflux distilling head

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

Procedure: A mixture of (S)-benzyl 2,3-epoxypropyl ether (8.95 g as described in Heterocycles Vol. 16, 381, 1981), o-cyclopropylmethoxyphenol (8.95 g) in 36 ml acetone and 4 ml hexane, to which is added powdered potassium carbonate (6.9 g), is stirred at reflux in nitrogen atmosphere for 74 hours. After cooling to room temperature the solid is filtered off and washed with acetone. The filtrate is concentrated under reduced pressure, the residue is dissolved in ether, the ether solution is washed 2x with water and dried over anhydrous sodium sulfate, filtered, and the filtrate is evaporated to dryness. The crude oil is distilled in vacuo, at 199°-212°/0.2 mm to yield (S)-1-benzyloxy-3-[o-(cyclopropylmethoxy)phenoxy]-2-hydroxypropane. at reflux in nitrogen atmosphere for 74 hours is filtered off washed with acetone The filtrate is concentrated under reduced pressure the residue is dissolved in ether the ether solution is washed 2x with water dried over anhydrous sodium sulfate filtered the filtrate is evaporated to dryness The crude oil is distilled in vacuo, at 199°-212°/0.2 mm