2-phenoxyacetaldehyde

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:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Methoxy-3-(trimethylsilyloxy)-1,3-butadiene (4.95 ml; 26 mmol) was added to a solution of phenoxyacetaldehyde (3.56 g, 26 mmol) in DCM (40 ml). The solution was cooled to −5° C. A 2.3 M solution of zinc chloride in DCM (5.6 ml, 13 mmol) was added. The reaction mixture was stirred for 16 hours, while it was warming up to room temperature. It was diluted with ethyl acetate (150 ml) and washed with a 10% aqueous solution of sodium hydrogensulphate (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate (100 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (200 g), using ethyl acetate/heptane (1:1) as eluent, to give 2.36 g of 2-phenoxymethyl-2,3-dihydropyran-4-one. was warming up to room temperature washed with a 10% aqueous solution of sodium hydrogensulphate (100 ml) The aqueous phase was extracted with ethyl acetate (100 ml) The combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate (100 ml) dried over magnesium sulphate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (200 g)

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

Procedure: At −78° C., a solution of dimethylsulphoxide (5.11 ml, 72 mmol) in DCM (50 ml) was added dropwise to a solution of oxalyl chloride (6.12 ml, 72 mmol) in DCM (150 ml). The reaction mixture was stirred for 10 min at −78° C. A solution of 2-phenoxyethanol (10.0 g, 72 mmol) in DCM (70 ml) was added dropwise. The reaction mixture was stirred at −78° C. for 10 min. A solution of triethylamine (50 ml, 360 mmol) in DCM (50 ml) was added dropwise. The reaction mixture was stirred for 10 min at −78° C. It was warmed to room temperature. The reaction mixture was washed with a 10% aqueous solution of sodium hydrogensulphate (2×200 ml) and subsequently with brine (2×200 ml). It was dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (100 g), using ethyl acetate/heptane (1:3) as eluent, to give 2.73 g of phenoxyacetaldehyde. The reaction mixture was stirred at −78° C. for 10 min The reaction mixture was stirred for 10 min at −78° C It was warmed to room temperature The reaction mixture was washed with a 10% aqueous solution of sodium hydrogensulphate (2×200 ml) and subsequently with brine (2×200 ml) It was dried over magnesium sulphate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (100 g)

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

Procedure: Sodium periodate (0.65 M in water, 20 mL) was added to a vigorously stirred suspension of silica gel (20 g) in dichloromethane (160 mL), followed by a solution of 3-phenoxy-1,2-propanediol (1.68 g, 10.0 mmol) in dichloromethane (20 mL). After stirring for 10 min the mixture was filtered and the filtrate was concentrated to give the subtitle compound (1.36 g, 100%). was filtered the filtrate was concentrated

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

Procedure: 2-Phenoxyacetaldehyde (1.36 g, 10 mmol) was added to a suspension of anhydrous magnesium sulfate (2.65 g, 22 mmol) in nitroethane (7.0 mL) under an argon atmosphere. After 5 min a solution of 2,8,9-triisopropyl-2,5,8,9-tetraaza-1-phosphabicyclo[3,3,3]undecane (0.30 g, 1.0 mmol) in nitromethane (3.0 mL) was added. The mixture was vigorously stirred for 5 days at r.t., filtered through celite and concentrated. Purification by column chromatography (SiO2, dichloromethane/t-butyl methyl ether) gave the subtitle compound as an oil (1.7 g, 81%). filtered through celite and concentrated Purification by column chromatography (SiO2, dichloromethane/t-butyl methyl ether)

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

Procedure: 2-Phenoxyacetaldehyde (1.36 g, 10 mmol) was added to a suspension of anhydrous magnesium sulfate (2.65 g, 22 mmol) in nitroethane (7.0 mL) under an argon atmosphere. After 5 min a solution of 2,8,9-triisopropyl-2,5,8,9-tetraaza-1-phosphabicyclo[3,3,3]undecane (0.30 g, 1.0 mmol) in nitromethane (3.0 mL) was added. The mixture was vigorously stirred for 5 days at r.t., filtered through celite and concentrated. Purification by column chromatography (SiO2, dichloromethane/t-butyl methyl ether) gave the subtitle compound as an oil (1.7 g, 81%). filtered through celite and concentrated Purification by column chromatography (SiO2, dichloromethane/t-butyl methyl ether)

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

Procedure: 2-Formylvinyl phenyl ether is prepared by treating phenoxyacetaldehyde with formaldehyde and diethylamine hydrochloride salt. The ether is then reacting with a solution of diethylphosphonoacetic acid and n-butyllithium in anhydrous tetrahydrofuran (THF) to form 5-phenoxy-2,4-pentadienoic acid. 5-Phenyl-2,4-pentadienal is obtained by first converting the carboxylic acid to a Weinreb amide using oxalyl chloride followed by N,O-dimethylhydroxylamine. Subsequently, reduction of the Weinreb amide with lithium aluminum hydride (LAH) in THF leads to the formation of 5-phenoxy-2,4-pentadienal. The synthesis is summarized in Scheme II.

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

Procedure: 12.8 g of 1-amino-2,6-dimethylpiperidine, 5.4 g of sodium cyanide and 15.0 g of phenoxyacetaldehyde are reacted analogously to 8a). 20.8 g of 2-(2,6-dimethylpiperidino)amino-3-phenoxypropionitrile are obtained, which are employed in the following step without further purification

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

Procedure: 2-Formylvinyl phenyl ether is prepared by treating phenoxyacetaldehyde with formaldehyde and diethylamine hydrochloride salt. The ether is then reacting with a solution of diethylphosphonoacetic acid and n-butyllithium in anhydrous tetrahydrofuran (THF) to form 5-phenoxy-2,4-pentadienoic acid. 5-Phenoxy-2,4-pentadienal is obtained by first converting the carboxylic acid to a Weinreb amide using oxalyl chloride followed by N,O-dimethylhydroxylamine. Subsequently, reduction of the Weinreb amide with lithium aluminum hydride (LAH) in THF leads to the formation of 5-phenoxy-2,4-pentadienal. The synthesis is summarized in Scheme II.

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Methoxy-3-(trimethylsilyloxy)-1,3-butadiene (4.95 ml; 26 mmol) was added to a solution of phenoxyacetaldehyde (3.56 g, 26 mmol) in DCM (40 ml). The solution was cooled to −5° C. A 2.3 M solution of zinc chloride in DCM (5.6 ml, 13 mmol) was added. The reaction mixture was stirred for 16 hours, while it was warming up to room temperature. It was diluted with ethyl acetate (150 ml) and washed with a 10% aqueous solution of sodium hydrogensulphate (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate (100 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (200 g), using ethyl acetate/heptane (1:1) as eluent, to give 2.36 g of 2-phenoxymethyl-2,3-dihydropyran-4-one. was warming up to room temperature washed with a 10% aqueous solution of sodium hydrogensulphate (100 ml) The aqueous phase was extracted with ethyl acetate (100 ml) The combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate (100 ml) dried over magnesium sulphate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (200 g)