5-phenylpentanal

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:0.00; pressure:0.00; stir:

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: A vigorously stirred solution of 5-phenylpentanol (10 g), sodium bromide (6.45 g) and TEMPO, 2,2,6,6-tetramethyl-1-piperidinyloxy, (0.095 g) in a mixture of ethyl acetate, toluene and water (258 ml, 7:7:1, v/v/v), at 0° C., was treated with aqueous sodium hypochlorite solution (571 ml, 0.35M) saturated with sodium bicarbonate (43.85 g) in five portions separated by 10 minute intervals. The reaction mixture was treated with ethanol (20 ml) then partitioned between water (500 ml) and ethyl acetate (500 ml). The aqueous layer was extracted twice with ethyl acetate (500 ml). The combined organic phases were washed with aqueous sodium thiosulphate (500 ml, 5%), then with water (200 ml), then with brine (200 ml), then dried over magnesium sulphate and then evaporated to give the title compound as an orange oil, which was used without further purification. NMR (CDCl3): δ1.65 (m,4H), 2.35 (m,2H), 2.60 (t,2H), 7.10-7.30 (m,5H), 9.75 (s,1H). separated by 10 minute intervals The reaction mixture was treated with ethanol (20 ml) then partitioned between water (500 ml) and ethyl acetate (500 ml) The aqueous layer was extracted twice with ethyl acetate (500 ml) The combined organic phases were washed with aqueous sodium thiosulphate (500 ml, 5%) with water (200 ml), then with brine (200 ml), then dried over magnesium sulphate evaporated

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

Procedure: A stirred solution of 5-phenylpentanal (9.96 g, Reference Example 6) in anhydrous tetrahydrofuran (100 ml) at room temperature was treated with (tert-butoxycarbonylmethylene)triphenylphosphorane (27.5 g). The resulting orange solution was stirred for 2.5 hours then evaporated. The residual crude product was subjected to flash chromatography on silica eluting with a mixture of hexane and ethyl acetate (19:1, v/v) to afford the title compound (12.4 g) as a colourless oil. NMR (CDCl3): δ1.45 (s,9H), 1.65 (m,4H), 2.18 (q,2H), 2.61 (t,2H), 5.70 (d,1H), 6.82 (dt,1H), 7.10-7.30 (m,5H). then evaporated The residual crude product was subjected to flash chromatography on silica eluting with a mixture of hexane and ethyl acetate (19:1

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

Procedure: To a solution of 1.61 g (5.0 mmol) of 3-[4-(imidazo[1,2-a]pyridin-5-ylthio)butyl]thiazolidine-2,4-dione and 4.2 g (10 mmol) of 5-phenylpentanal in 20 ml of ethanol, 0.05 ml (0.5 mmol) of piperidine was added, followed by refluxing for 2.5 hours. After the reaction mixture was cooled, the solvent was distilled off. The residue was dissolved in chloroform, washed with water and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent, n-hexane/ethyl acetate=1/4) to yield 2.627 g (quant., brown oily substance) of the desired product. by refluxing for 2.5 hours After the reaction mixture was cooled the solvent was distilled off The residue was dissolved in chloroform washed with water dried after which the solvent was distilled off The residue was purified by column chromatography (eluent, n-hexane/ethyl acetate=1/4)

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triethyl-2-phosphonopropionate (12 g, 50 mmol) and 5-phenylpentanal (7 g, 43 mmol) are dissolved in dry THF (100 mL) and cooled to 10° C. A solution of sodium ethoxide in ethanol (23 mL, 21%, 43 mmol) is added slowly over 20 minutes and the reaction is warmed to 23° C. After stirring 1 hour, the reaction is quenched by the addition of a saturated NH4Cl solution (30 mL). The reaction is concentrated to remove the THF in vacuo, diluted with petroleum ether (400 mL) and washed with 1 N HCl (100 mL), H2O (100 mL), NaHCO3 (100 mL), brine (100 mL) and dried (MgSO4). The solution is concentrated in vacuo and purified by filtration through a plug of silica gel using 2% ether/pet ether as the eluant to yield (E)-ethyl 2-methyl-7-phenylhept-2-enoate, (8.9 g, 84%) which contains a small amount (10%) of the Z-isomer: 1H NMR (CDCl3) δ 7.29-7.23 (m, 2H), 7.19-7.14 (m, 3H), 6.75 (dt, J=15.5, 1.5 Hz, 1H), 4.18 (q, J=7.1 Hz, 2H), 2.62 (t, J=7.5 Hz, 2H), 2.18 (q, J=7.0 Hz, 2H), 1.81 (s, 3H), 1.70-1.59 (m, 2H), 1.54-1.42 (m. 2H), 1.28 (t, J=7.1 Hz, 3H); MS (FAB) m/e 247 (M+H)+. the reaction is warmed to 23° C the reaction is quenched by the addition of a saturated NH4Cl solution (30 mL) The reaction is concentrated to remove the THF in vacuo diluted with petroleum ether (400 mL) washed with 1 N HCl (100 mL), H2O (100 mL), NaHCO3 (100 mL), brine (100 mL) dried (MgSO4) The solution is concentrated in vacuo purified by filtration through a plug of silica gel using 2% ether/pet ether as the eluant

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triethyl-2-phosphonopropionate (12 g, 50 mmol) and 5-phenylpentanal (7 g, 43 mmol) are dissolved in dry THF (100 mL) and cooled to 10° C. A solution of sodium ethoxide in ethanol (23 mL, 21%, 43 mmol) is added slowly over 20 minutes and the reaction is warmed to 23° C. After stirring 1 hour, the reaction is quenched by the addition of a saturated NH4Cl solution (30 mL). The reaction is concentrated to remove the THF in vacuo, diluted with petroleum ether (400 mL) and washed with 1 N HCl (100 mL), H2O (100 mL), NaHCO3 (100 mL), brine (100 mL) and dried (MgSO4). The solution is concentrated in vacuo and purified by filtration through a plug of silica gel using 2% ether/pet ether as the eluant to yield (E)-ethyl 2-methyl-7-phenylhept-2-enoate, (8.9 g, 84%) which contains a small amount (10%) of the Z-isomer: 1H NMR (CDCl3) δ 7.29-7.23 (m, 2H), 7.19-7.14 (m, 3H), 6.75 (dt, J=15.5, 1.5 Hz, 1H), 4.18 (q, J=7.1 Hz, 2H), 2.62 (t, J=7.5 Hz, 2H), 2.18 (q, J=7.0 Hz, 2H), 1.81 (s, 3H), 1.70-1.59 (m, 2H), 1.54-1.42 (m. 2H), 1.28 (t, J=7.1 Hz, 3H); MS (FAB) m/e 247 (M+H)+. the reaction is warmed to 23° C the reaction is quenched by the addition of a saturated NH4Cl solution (30 mL) The reaction is concentrated to remove the THF in vacuo diluted with petroleum ether (400 mL) washed with 1 N HCl (100 mL), H2O (100 mL), NaHCO3 (100 mL), brine (100 mL) dried (MgSO4) The solution is concentrated in vacuo purified by filtration through a plug of silica gel using 2% ether/pet ether as the eluant

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

Procedure: t-Butyl acrylate (6.7 g, 46 mmol), 5-phenyl pentanal (3.7 g, 23 mmol) and 3-quinuclidinol (0.38 g, 3 mmol) are combined and stirred under N2. After 24 hours stirring is halted and the resulting solution is allowed to sit at ambient temperature for 16 days. TLC analysis (30% ether in petroleum ether) showed that the reaction is nearly complete. The product is purified by column chromatography (silica, 20% ether in petroleum ether) to yield t-butyl 2-(1-hydroxy-5-phenylpentyl)acrylate (6 g, 45%): 1H NMR (300 MHz, CDCl3) δ 7.29-7.24 (m, 2H), 7.18-7.14 (m, 3H), 6.10 (d, J=1.1 Hz, 1H), 5.67 (s, 1H), 4.33 (q, J=6.7 Hz, 1H), 2.74 (d, J=6.7 Hz, 1H), 2.61 (t, J=7.6 Hz, 2H), 1.70-1.53 (m, 4H), 1.50 (s, 9H), 1.50-1.32 (m, 2H); 13C NMR (75.5 MHz, CDCl3) δ 165.93, 143.91, 142.51, 128.32, 128.20, 125.57, 123.82, 81.35, 71.79, 36.17, 35.82, 31.26, 28.04, 25.54; MS (EI) m/e 291 (M+H)+. After 24 hours stirring The product is purified by column chromatography (silica, 20% ether in petroleum ether)