3,4-dihydro-2H-pyran-2-carbaldehyde

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

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

Procedure: Menthol may be condensed with compound 16, 3,4-dihydro-2H-pyran-2-carboxaldeyde in the presence of acid to provide compound 17, 6-menthyloxy-tetrahydro-2H-pyran-2-carboxaldehyde. A Lewis acid or a protic acid may be employed, with protic acids being preferred. Aldehyde 17 may be reduced to an alcohol 19, 6-menthyloxy-tetrahydro-2H-pyran-2-methanol, by catalytic hydrogeneration for example, over Raney nickel or a nobel metal catalyst. Compound 17 may alternatively be reduced to compound 19 using a hydride reducing agent, such as sodium borohydride or lithium aluminum hydride.

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

Procedure: 8.75 G. (0.20 mole) of 55 percent sodium hydride dispersion was washed under nitrogen with dry pentane to remove the mineral oil. To the flask was added 600 ml. of dimethylsulfoxide (dried over Linde 3A molecular sieves). The resulting suspension was carefully degassed, placed under nitrogen, and heated at 70°-75° for 1 hour. The gray-green solution was cooled to approximately 15° and 91.6 g. (0.20 mole) of (3,5-dimethyl-4-isoxazolylmethyl)triphenylphosphonium chloride, prepared as described in Example 4 above, was added in one portion. After approximately 5 minutes, a bright orange precipitate formed in the initially dark red solution. This suspension was stirred at room temperature for 45 minutes. To the mixture was then added, drop-wise via syringe, 25.0 g. (0.223 mole) of acrolein dimer (freshly distilled from and into hydroquinone) at such a rate that the temperature remained less than 30° (10-15 minutes with water bath cooling). The light orange-brown solution was stirred at room temperature for 20 minutes, and then at 60°-65° for 3 hours. (In some experiments, the mixture became very black during the heating period). The reaction mixture was cooled, poured onto ice, and slurried until all of the dark oil solidified. The suspension was filtered and the filter cake was washed well with pentane. The filtrates were extracted with pentane and the pentane solutions were washed with water and brine and dried over anhydrous sodium sulfate. Solvent removal gave a slightly orange oil which was distilled from a small quantity of anhydrous potassium carbonate to give the desired product as a colorless liquid, b.p. 83°-85°/0.1 mm. A similarly prepared sample of b.p. 77°-85°/0.5 mm. was submitted for analysis. to remove the mineral oil To the flask was added 600 ml The resulting suspension was carefully degassed heated at 70°-75° for 1 hour The gray-green solution was cooled to approximately 15° was added in one portion a bright orange precipitate formed in the initially dark red solution To the mixture was then added remained less than 30° The light orange-brown solution was stirred at room temperature for 20 minutes at 60°-65° for 3 hours The reaction mixture was cooled poured onto ice The suspension was filtered the filter cake was washed well with pentane The filtrates were extracted with pentane the pentane solutions were washed with water and brine dried over anhydrous sodium sulfate Solvent removal gave a slightly orange oil which was distilled from a small quantity of anhydrous potassium carbonate

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

Procedure: 8.75 G. (0.20 mole) of 55 percent sodium hydride dispersion was washed under nitrogen with dry pentane to remove the mineral oil. To the flask was added 600 ml. of dimethylsulfoxide (dried over Linde 3A molecular sieves). The resulting suspension was carefully degassed, placed under nitrogen, and heated at 70°-75° for 1 hour. The gray-green solution was cooled to approximately 15° and 91.6 g. (0.20 mole) of (3,5-dimethyl-4-isoxazolylmethyl)triphenylphosphonium chloride, prepared as described in Example 4 above, was added in one portion. After approximately 5 minutes, a bright orange precipitate formed in the initially dark red solution. This suspension was stirred at room temperature for 45 minutes. To the mixture was then added, drop-wise via syringe, 25.0 g. (0.223 mole) of acrolein dimer (freshly distilled from and into hydroquinone) at such a rate that the temperature remained less than 30° (10-15 minutes with water bath cooling). The light orange-brown solution was stirred at room temperature for 20 minutes, and then at 60°-65° for 3 hours. (In some experiments, the mixture became very black during the heating period). The reaction mixture was cooled, poured onto ice, and slurried until all of the dark oil solidified. The suspension was filtered and the filter cake was washed well with pentane. The filtrates were extracted with pentane and the pentane solutions were washed with water and brine and dried over anhydrous sodium sulfate. Solvent removal gave a slightly orange oil which was distilled from a small quantity of anhydrous potassium carbonate to give the desired product as a colorless liquid, b.p. 83°-85°/0.1 mm. A similarly prepared sample of b.p. 77°-85°/0.5 mm. was submitted for analysis. to remove the mineral oil To the flask was added 600 ml The resulting suspension was carefully degassed heated at 70°-75° for 1 hour The gray-green solution was cooled to approximately 15° was added in one portion a bright orange precipitate formed in the initially dark red solution To the mixture was then added remained less than 30° The light orange-brown solution was stirred at room temperature for 20 minutes at 60°-65° for 3 hours The reaction mixture was cooled poured onto ice The suspension was filtered the filter cake was washed well with pentane The filtrates were extracted with pentane the pentane solutions were washed with water and brine dried over anhydrous sodium sulfate Solvent removal gave a slightly orange oil which was distilled from a small quantity of anhydrous potassium carbonate

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

Procedure: 3-Imidazol-1-yl-propylamine (1 mmol) and 3,4-Dihydro-2H-pyran-2-carbaldehyde (1 mmol) were combined in methanol (2 ml, dry). After 2 hours Trimethylsilylazide (5 mmol) and (2-Isocyano-ethyl)-dimethyl-amine (1 mmol) was added. The reaction was stirred at room temperature for 48 h. After evaporation of the solvent the residue was purified with chromatographic methods. After evaporation of the solvent the residue was purified with chromatographic methods

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

Procedure: 3-Imidazol-1-yl-propylamine (1 mmol) and 3,4-Dihydro-2H-pyran-2-carbaldehyde (1 mmol) were combined in methanol (2 ml, dry). After 2 hours Trimethylsilylazide (5 mmol) and Isocyano-cyclopentan (1 mmol) was added. The reaction was stirred at room temperature for 48 h. After evaporation of the solvent the residue was purified with chromatographic methods. After evaporation of the solvent the residue was purified with chromatographic methods

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

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

Procedure: 3-Imidazol-1-yl-propylamine (1 mmol) and 3,4-Dihydro-2H-pyran-2-carbaldehyde (1 mmol) were combined in methanol (2 ml, dry). After 2 hours Trimethylsilylazide (5 mmol) and (2-Isocyano-ethyl)-dimethyl-amine (1 mmol) was added. The reaction was stirred at room temperature for 48 h. After evaporation of the solvent the residue was purified with chromatographic methods. After evaporation of the solvent the residue was purified with chromatographic methods

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

Procedure: 3-Imidazol-1-yl-propylamine (1 mmol) and 3,4-Dihydro-2H-pyran-2-carbaldehyde (1 mmol) were combined in methanol (2 ml, dry). After 2 hours Trimethylsilylazide (5 mmol) and Isocyano-cyclopentan (1 mmol) was added. The reaction was stirred at room temperature for 48 h. After evaporation of the solvent the residue was purified with chromatographic methods. After evaporation of the solvent the residue was purified with chromatographic methods

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,4-Dihydro-2H-pyran-2-carbaldehyde (300 g, 2.68 mol) was dissolved in tetrahydrofuran (710 mL). Raney-Co catalyst (30 g, tetrahydrofuran moist) was added. Gaseous methyl amine (415.4 g, 13.4 mol) was transferred into the solution within 50 minutes (45° C.). Hydrogen (49.2 L) was added and the pressure adjusted to 100 bar and the solution was stirred for about 2 h at 100° C. The reaction vessel was cooled to room temperature, the gas removed and the solution degassed. The solution was concentrated under reduced pressure. The crude product (344.5 g) was distilled at reduced pressure to receive (3,4-Dihydro-2H-pyran-2-ylmethyl)-methyl-amine (289.8 g, 2.28 mol, 85% yield). Analytical data amine (3,4-Dihydro-2H-pyran-2-ylmethyl)-methyl-amine: Bp. 55-57° C. at 16 mbar; HPLC-MS: (M+H)+=128 at rt=0.619 min. (TIC), rt=0.596 min. (UV), rt=0.631 min. (ELS), Chromolith SpeedROD RP-18e 50-4.6 mm, solvent A: water+0.1% TFA, solvent B: acetonitrile+0.1% TFA, gradient: 4% solvent B at 0.0 min., 100% solvent B at 2.6 min., flow: 2.4 mL/min., UV: 220 nm. (45° C.) The reaction vessel was cooled to room temperature the gas removed the solution degassed The solution was concentrated under reduced pressure The crude product (344.5 g) was distilled at reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Imidazol-1-yl-propylamine (1 mmol) and 3,4-Dihydro-2H-pyran-2-carbaldehyde (1 mmol) were added to ethanol (5 ml). After 30 min 3-(4-Hydroxy-phenyl)-2-oxo-propionic acid ethyl ester (1 mmol) was added. The reaction was heated to 50° C. and stirred for 24 h. After evaporation of the solvent the residue was purified with chromatographic methods. After evaporation of the solvent the residue was purified with chromatographic methods

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Imidazol-1-yl-propylamine (1 mmol) and 3,4-Dihydro-2H-pyran-2-carbaldehyde (1 mmol) were added to ethanol (5 ml). After 30 min 3-(1H-Indol-3-yl)-2-oxo-propionic acid ethyl ester (1 mmol) was added. The reaction was heated to 50° C. and stirred for 24 h. After evaporation of the solvent the residue was purified with chromatographic methods. After evaporation of the solvent the residue was purified with chromatographic methods