7-phenoxyheptanal

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

Procedure: To a stirred solution of 63 (0.252 g, 3 mmol) in anhydrous THF (5 mL), at −78° C., under a nitrogen atmosphere, was added n-BuLi (1.2 mL, 3 mmol, using a 2.5 M solution in hexanes) dropwise. Stirring was continued for 15 min at −78° C. and then MgBr2.Et2O (0.774 g, 3 mmol) was added. The resulting mixture was warmed to −50° C. over a 2 hours period, and then it was transferred by cannula to a cooled (−78° C.) slurry of 62.1 (0.125 g, 0.6 mmol) and CeCl3, (0.738 g, 3 mmol) in anhydrous THF (6 mL), which was previously stirred at room temperature for 2 hours under nitrogen. Following the addition, the resultant mixture was allowed to warm to room temperature over a 4 hours period. The reaction mixture was quenched with dropwise addition of 5% aqueous AcOH solution (10 mL), diluted with AcOEt (20 mL) and the organic phase was separated. The aqueous layer extracted with AcOEt, the combined organic layer was washed with aqueous saturated NaHCO3 solution and brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue obtained was purified by flash column chromatography on silica gel (75% ethyl acetate-hexane) to give 64.1 (92.5 mg, 53% yield) as a white solid (m p 50-52° C.). was previously stirred at room temperature for 2 hours under nitrogen the addition to warm to room temperature over a 4 hours period The reaction mixture was quenched with dropwise addition of 5% aqueous AcOH solution (10 mL) diluted with AcOEt (20 mL) the organic phase was separated The aqueous layer extracted with AcOEt the combined organic layer was washed with aqueous saturated NaHCO3 solution and brine dried (MgSO4) the solvent was evaporated under reduced pressure The residue obtained was purified by flash column chromatography on silica gel (75% ethyl acetate-hexane)

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

Procedure: To a stirred solution of 63 (0.252 g, 3 mmol) in anhydrous THF (5 mL), at −78° C., under a nitrogen atmosphere, was added n-BuLi (1.2 mL, 3 mmol, using a 2.5 M solution in hexanes) dropwise. Stirring was continued for 15 min at −78° C. and then MgBr2.Et2O (0.774 g, 3 mmol) was added. The resulting mixture was warmed to −50° C. over a 2 hours period, and then it was transferred by cannula to a cooled (−78° C.) slurry of 62.1 (0.125 g, 0.6 mmol) and CeCl3, (0.738 g, 3 mmol) in anhydrous THF (6 mL), which was previously stirred at room temperature for 2 hours under nitrogen. Following the addition, the resultant mixture was allowed to warm to room temperature over a 4 hours period. The reaction mixture was quenched with dropwise addition of 5% aqueous AcOH solution (10 mL), diluted with AcOEt (20 mL) and the organic phase was separated. The aqueous layer extracted with AcOEt, the combined organic layer was washed with aqueous saturated NaHCO3 solution and brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue obtained was purified by flash column chromatography on silica gel (75% ethyl acetate-hexane) to give 64.1 (92.5 mg, 53% yield) as a white solid (m p 50-52° C.). was previously stirred at room temperature for 2 hours under nitrogen the addition to warm to room temperature over a 4 hours period The reaction mixture was quenched with dropwise addition of 5% aqueous AcOH solution (10 mL) diluted with AcOEt (20 mL) the organic phase was separated The aqueous layer extracted with AcOEt the combined organic layer was washed with aqueous saturated NaHCO3 solution and brine dried (MgSO4) the solvent was evaporated under reduced pressure The residue obtained was purified by flash column chromatography on silica gel (75% ethyl acetate-hexane)

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

Procedure: 7-[4-(Benzyloxy)phenoxy]heptanal 62.2 was synthesized analogous to the preparation of 62.1 using 61.2/20.4 (0.624 g, 2 mmol) and diisobutylaluminum hydride (4.5 mL, 4.5 mmol, using a 1M solution in hexanes) in THF (20 mL). Purification by flash column chromatography on silica gel gave 62.2 (0.39 g, 63% yield) as a white solid (m p 65-67° C.). Purification by flash column chromatography on silica gel

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

Procedure: To a stirred solution of 61.1 (0.56 g, 2.24 mmol) in dry THF (20 mL), at −78° C., under a nitrogen atmosphere was added diisobutylaluminum hydride (5 mL, 5 mmol, using a 1M solution in hexanes) dropwise. The reaction mixture was stirred at the same temperature for 30 min and then quenched by dropwise addition of potassium sodium tartrate (10% solution in water). The resulting mixture was warmed to room temperature and stirred vigorously for 1 h. The organic layer was separated and the aqueous phase extracted with diethyl ether. The combined organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with 25% diethyl ether-hexane to give 62.1 (0.26 g, 65% yield) as a colorless viscous liquid. quenched by dropwise addition of potassium sodium tartrate (10% solution in water) stirred vigorously for 1 h The organic layer was separated the aqueous phase extracted with diethyl ether The combined organic layer was washed with brine dried (MgSO4) concentrated in vacuo The residue was purified by column chromatography on silica gel eluting with 25% diethyl ether-hexane

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

Procedure: To a stirred solution of 63 (0.252 g, 3 mmol) in anhydrous THF (5 mL), at −78° C., under a nitrogen atmosphere, was added n-BuLi (1.2 mL, 3 mmol, using a 2.5 M solution in hexanes) dropwise. Stirring was continued for 15 min at −78° C. and then MgBr2.Et2O (0.774 g, 3 mmol) was added. The resulting mixture was warmed to −50° C. over a 2 hours period, and then it was transferred by cannula to a cooled (−78° C.) slurry of 62.1 (0.125 g, 0.6 mmol) and CeCl3, (0.738 g, 3 mmol) in anhydrous THF (6 mL), which was previously stirred at room temperature for 2 hours under nitrogen. Following the addition, the resultant mixture was allowed to warm to room temperature over a 4 hours period. The reaction mixture was quenched with dropwise addition of 5% aqueous AcOH solution (10 mL), diluted with AcOEt (20 mL) and the organic phase was separated. The aqueous layer extracted with AcOEt, the combined organic layer was washed with aqueous saturated NaHCO3 solution and brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue obtained was purified by flash column chromatography on silica gel (75% ethyl acetate-hexane) to give 64.1 (92.5 mg, 53% yield) as a white solid (m p 50-52° C.). was previously stirred at room temperature for 2 hours under nitrogen the addition to warm to room temperature over a 4 hours period The reaction mixture was quenched with dropwise addition of 5% aqueous AcOH solution (10 mL) diluted with AcOEt (20 mL) the organic phase was separated The aqueous layer extracted with AcOEt the combined organic layer was washed with aqueous saturated NaHCO3 solution and brine dried (MgSO4) the solvent was evaporated under reduced pressure The residue obtained was purified by flash column chromatography on silica gel (75% ethyl acetate-hexane)

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

Procedure: 7-[4-(Benzyloxy)phenoxy]heptanal 62.2 was synthesized analogous to the preparation of 62.1 using 61.2/20.4 (0.624 g, 2 mmol) and diisobutylaluminum hydride (4.5 mL, 4.5 mmol, using a 1M solution in hexanes) in THF (20 mL). Purification by flash column chromatography on silica gel gave 62.2 (0.39 g, 63% yield) as a white solid (m p 65-67° C.). Purification by flash column chromatography on silica gel

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

Procedure: To a stirred solution of 61.1 (0.56 g, 2.24 mmol) in dry THF (20 mL), at −78° C., under a nitrogen atmosphere was added diisobutylaluminum hydride (5 mL, 5 mmol, using a 1M solution in hexanes) dropwise. The reaction mixture was stirred at the same temperature for 30 min and then quenched by dropwise addition of potassium sodium tartrate (10% solution in water). The resulting mixture was warmed to room temperature and stirred vigorously for 1 h. The organic layer was separated and the aqueous phase extracted with diethyl ether. The combined organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with 25% diethyl ether-hexane to give 62.1 (0.26 g, 65% yield) as a colorless viscous liquid. quenched by dropwise addition of potassium sodium tartrate (10% solution in water) stirred vigorously for 1 h The organic layer was separated the aqueous phase extracted with diethyl ether The combined organic layer was washed with brine dried (MgSO4) concentrated in vacuo The residue was purified by column chromatography on silica gel eluting with 25% diethyl ether-hexane