5-phenylmethoxypentanal

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: Under a nitrogen atmosphere a mixture of 8.0 grams (0.041 mole) of 7-phenyl-6-oxaheptan-1-ol and 1.4 grams of 95% silicon dioxide in 125 ml of methylene chloride was stirred, and 19.8 grams (0.090 mole) of pyridinium chlorochromate was added. Upon completion of addition, the reaction mixture was stirred at ambient temperature for four hours. After this time the reaction mixture was diluted with diethyl ether and then was passed through a column of magnesium silicate. The eluate was concentrated under reduced pressure yielding 6.2 grams of 7-phenyl-6-oxaheptan-1-al. The reaction was repeated. Upon completion of addition the reaction mixture was stirred at ambient temperature for four hours The eluate was concentrated under reduced pressure

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

Procedure: Under a nitrogen atmosphere a mixture of 8.0 grams (0.041 mole) of 7-phenyl-6-oxaheptan-1-ol and 1.4 grams of 95% silicon dioxide in 125 ml of methylene chloride was stirred, and 19.8 grams (0.090 mole) of pyridinium chlorochromate was added. Upon completion of addition, the reaction mixture was stirred at ambient temperature for four hours. After this time the reaction mixture was diluted with diethyl ether and then was passed through a column of magnesium silicate. The eluate was concentrated under reduced pressure yielding 6.2 grams of 7-phenyl-6-oxaheptan-1-al. The reaction was repeated. Upon completion of addition the reaction mixture was stirred at ambient temperature for four hours The eluate was concentrated under reduced pressure

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

Procedure: Another multi-step synthesis of ethers started with the reaction of a commercially available alkylene diol, e.g., 1,6-pentanediol, with an alkyl or aralkyl halide, e.g., phenylmethyl bromide, in the presence of potassium hydroxide in xylene solvent, yielding 7-phenyl-6-oxaheptan-1-ol (XVI). Oxidation of (XVI) with pyridinium chlorochromate produced the corresponding aldehyde, 7-phenyl-6-oxaheptanal (XVII). Reaction of (XVII) with dibromodifluoromethane, triphenylphosphine, and powdered zinc in dimethylacetamide provided 6,6-difluoro-5-hexenyl phenylmethyl ether (XVIII). This synthesis is detailed in Example 11.

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

Procedure: Another multi-step synthesis of ethers started with the reaction of a commercially available alkylene diol, e.g., 1,6-pentanediol, with an alkyl or aralkyl halide, e.g., phenylmethyl bromide, in the presence of potassium hydroxide in xylene solvent, yielding 7-phenyl-6-oxaheptan-1-ol (XVI). Oxidation of (XVI) with pyridinium chlorochromate produced the corresponding aldehyde, 7-phenyl-6-oxaheptanal (XVII). Reaction of (XVII) with dibromodifluoromethane, triphenylphosphine, and powdered zinc in dimethylacetamide provided 6,6-difluoro-5-hexenyl phenylmethyl ether (XVIII). This synthesis is detailed in Example 11.

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

Procedure: The alcohol obtained in Step 1 (20.0 mmol) was dissolved in CH2Cl2 (100 mL). Dess-Martin periodinane (8.70 g, 20.5 mmol, 1 equiv.) was added, and the resulting solution stirred at room temperature for 18 h. The reaction mixture was then diluted with sat. aq. NaHCO3 (50 mL) and sat. aq. NaS2O3 (50 mL). The layers were separated, and the aqueous layer extracted with CH2Cl2 (2×100 mL. The combined organic layers were washed with sat. aq. NaHCO3 (100 mL) and brine (2×100 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, EtOAc:pet ether=1:2 to 2:3) to give the resulting aldehyde (2.85 g, 14.8 mmol, 75% yield from the alcohol) as a colorless oil. 1H NMR (500 MHz, CDCl3) δ=9.76 (t, J=1.7 Hz, 1H), 7.37-7.26 (m, 5H), 4.50 (s, 2H), 3.49 (t, J=6.2 Hz, 2H), 2.46 (td, J=7.2, 1.8 Hz, 2H), 1.79-1.71 (m, 2H), 1.70-1.61 (m, 2H) ppm; 13C NMR (125 MHz, CDCl3) δ=202.6, 138.7, 128.6, 127.84, 127.79, 73.2, 70.0, 43.8, 29.4, 19.2 ppm; LRMS (ESI+ve): 215 (M+Na+). The layers were separated the aqueous layer extracted with CH2Cl2 (2×100 mL The combined organic layers were washed with sat. aq. NaHCO3 (100 mL) and brine (2×100 mL) dried (MgSO4) filtered concentrated under reduced pressure The residue was purified by flash column chromatography (silica gel, EtOAc:pet ether=1:2 to 2:3)

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

Procedure: Under a nitrogen atmosphere a mixture of 8.0 grams (0.041 mole) of 7-phenyl-6-oxaheptan-1-ol and 1.4 grams of 95% silicon dioxide in 125 ml of methylene chloride was stirred, and 19.8 grams (0.090 mole) of pyridinium chlorochromate was added. Upon completion of addition, the reaction mixture was stirred at ambient temperature for four hours. After this time the reaction mixture was diluted with diethyl ether and then was passed through a column of magnesium silicate. The eluate was concentrated under reduced pressure yielding 6.2 grams of 7-phenyl-6-oxaheptan-1-al. The reaction was repeated. Upon completion of addition the reaction mixture was stirred at ambient temperature for four hours The eluate was concentrated under reduced pressure

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

Procedure: Another multi-step synthesis of ethers started with the reaction of a commercially available alkylene diol, e.g., 1,6-pentanediol, with an alkyl or aralkyl halide, e.g., phenylmethyl bromide, in the presence of potassium hydroxide in xylene solvent, yielding 7-phenyl-6-oxaheptan-1-ol (XVI). Oxidation of (XVI) with pyridinium chlorochromate produced the corresponding aldehyde, 7-phenyl-6-oxaheptanal (XVII). Reaction of (XVII) with dibromodifluoromethane, triphenylphosphine, and powdered zinc in dimethylacetamide provided 6,6-difluoro-5-hexenyl phenylmethyl ether (XVIII). This synthesis is detailed in Example 11.