cycloheptanecarbaldehyde

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: The title compound was prepared according to the procedure of Example 216, with the modification that cycloheptanecarboxaldehyde was used in step d instead of cyclohexanecarboxaldehyde and 5-amino-2-methyl-benzoic acid benzyl ester replaced 3-amino-benzoic acid benzyl ester in step f. 1H NMR (300 MHz, d6-DMSO) 12.40 (1H, br s), 12.11 (1H, br s), 9.55 (1H, s), 8.30 (1H, s), 7.76 (1H, d), 7.20 (1H, d), 4.78 (2H, s), 2.87 (1H, m), 2.45 (3H, s), 2.10-1.47 (27H, m). The acid was converted to the N-methyl-D-glucamine salt and lyophilised from water/dioxan. Found: C, 60.38; H, 8.36; N, 7.51%; C37H56N4O9.2.0 H2O requires: C, 60.31; H, 8.21; N, 7.60%.

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

Procedure: To a solution of 9.3 mg of piperidin-4-yl (2R)-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylethanoate in 1 ml of methanol, 10 mg of cycloheptanecarbaldehyde and then 0.5 ml of advancedly prepared 0.3 M methanol solution of sodium cyanoborohydride and zinc chloride (1:0.5) were added at room temperature, followed by 30 minutes' stirring at the same temperature. The reaction liquid was diluted with ethyl acetate, washed successively with saturated sodium hydrogenecarbonate solution and with saturated brine, and dried over anhydrous sodium sulfate. Distilling the solvent off under reduced pressure, the residue was purified on preparative thin layer chromatography (Kieselgel™60F254, Art5744 (Merck), chloroform/methanol=10/1) to provide the title compound. The reaction liquid washed successively with saturated sodium hydrogenecarbonate solution and with saturated brine dried over anhydrous sodium sulfate Distilling the solvent off under reduced pressure the residue was purified on preparative thin layer chromatography (Kieselgel™60F254, Art5744 (Merck), chloroform/methanol=10/1)

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: Cycloheptanemethanol (20 mmol, 2.56 g) was combined with methylene chloride (40 ml), Celite® (2.56 g), and MgSO4 (0.5 g). Pyridinium chlorochromate (30 mmol, 6.47 g) was added. After 2.5 hours, the mixture was filtered through silica and concentrated, affording the title compound as an oil (2.33 g, 91%). the mixture was filtered through silica concentrated

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

Procedure: To a solution of 9.3 mg of piperidin-4-yl (2R)-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylethanoate in 1 ml of methanol, 10 mg of cycloheptanecarbaldehyde and then 0.5 ml of advancedly prepared 0.3 M methanol solution of sodium cyanoborohydride and zinc chloride (1:0.5) were added at room temperature, followed by 30 minutes' stirring at the same temperature. The reaction liquid was diluted with ethyl acetate, washed successively with saturated sodium hydrogenecarbonate solution and with saturated brine, and dried over anhydrous sodium sulfate. Distilling the solvent off under reduced pressure, the residue was purified on preparative thin layer chromatography (Kieselgel™60F254, Art5744 (Merck), chloroform/methanol=10/1) to provide the title compound. The reaction liquid washed successively with saturated sodium hydrogenecarbonate solution and with saturated brine dried over anhydrous sodium sulfate Distilling the solvent off under reduced pressure the residue was purified on preparative thin layer chromatography (Kieselgel™60F254, Art5744 (Merck), chloroform/methanol=10/1)

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

Procedure: To a solution of 9.3 mg of piperidin-4-yl(2R)-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylethanoate in 1 ml of methanol, 10 mg of cycloheptanecarbaldehyde and then 0.5 ml of advancedly prepared 0.3 M methanol solution of sodium cyanoborohydride and zinc chloride (1:0.5) were added at room temperature, followed by 30 minutes' stirring at the same temperature. The reaction liquid was diluted with ethyl acetate, washed successively with saturated sodium hydrogenecarbonate solution and with saturated brine, and dried over anhydrous sodium sulfate. Distilling the solvent off under reduced pressure, the residue was purified on preparative thin layer chromatography (Kieselgel™60F254, Art5744 (Merck), chloroform/methanol=10/1) to provide the title compound. The reaction liquid washed successively with saturated sodium hydrogenecarbonate solution and with saturated brine dried over anhydrous sodium sulfate Distilling the solvent off under reduced pressure the residue was purified on preparative thin layer chromatography (Kieselgel™60F254, Art5744 (Merck), chloroform/methanol=10/1)

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

Procedure: To a stirred solution of 3-methoxy-2-(2,4,6-trimethyl-phenyl)-cyclopent-2-enone (0.46 g, 2.0 mmol) in anhydrous THF (20 ml) at −78 C under an N2 atmosphere was added dropwise a solution of lithium diisopropylamide (1.22 ml of a 1.8M solution in THF/heptanes/ethyl benzene, 2.2 mmol). The reaction was stirred at −78 C for 90 minutes and then a solution of cycloheptanecarbaldehyde (316 mg, 2.5 mmol) in anhydrous THF (3 ml) was added dropwise. The reaction was stirred at −78 C for a further 30 minutes and then allowed to warm to room temperature over 30 minutes. The reaction was quenched by addition of H2O (25 ml) and extracted with EtOAc (3×20 ml). The combined organic extracts were washed with brine (15 ml), dried over MgSO4, filtered and evaporated to dryness under reduced pressure to give a brown oil (628 mg). The crude material was purified by flash chromatography over SiO2 using a 100% isohexane to 100% EtOAc gradient to give the desired product as a colourless oil (101 mg). The reaction was stirred at −78 C for a further 30 minutes The reaction was quenched by addition of H2O (25 ml) extracted with EtOAc (3×20 ml) The combined organic extracts were washed with brine (15 ml) dried over MgSO4 filtered evaporated to dryness under reduced pressure

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

Procedure: To a stirred solution of cycloheptyl-methanol (1.28 g, 0.01 mol) in CH2Cl2 (50 ml) at room temperature was added portionwise PCC (3.23 g, 0.015 mol). The reaction turned almost instantly dark brown as was stirred at room temperature for 4 hours. The reaction was then diluted with Et2O (50 ml) and the solvent decanted away from the solid residue. The residue was washed with further Et2O (2×25 ml). The reaction mixture and combined washing were then filtered through a 10 g SiO2 chromatography cartridge and washed through with further Et2O (25 ml). The solvent was then removed under reduced pressure to yield the desired compound (1.08 g) as a colourless, pungent oil which was used without further purification. the solvent decanted away from the solid residue The residue was washed with further Et2O (2×25 ml) The reaction mixture and combined washing were then filtered through a 10 g SiO2 chromatography cartridge washed through with further Et2O (25 ml) The solvent was then removed under reduced pressure

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

Procedure: 34 mg of N-(piperidin-4-yl)-2-cyclopentyl-2-hydroxy-2-phenylacetamide obtained in Step 2 of Example 27, 50 mg of cycloheptanecarbaldehyde and 10 mg of acetic acid were dissolved in tetrahydrofuran. 70 mg of sodium triacetoxyborohydride was added thereto and the resulting mixture was stirred for 17 hours. After the addition of a saturated aqueous solution of sodium bicarbonate, the reaction mixture was extracted with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. After the solvent was distilled off under reduced pressure, the resulting residue was purified by preparative thin layer chromatography (Kieselgel™, 60F254, Art 5744 (manufactured by E. Merck; developing solvent: chloroform/methanol=10/1) to obtain the title compound. the reaction mixture was extracted with chloroform The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate After the solvent was distilled off under reduced pressure the resulting residue was purified by preparative thin layer chromatography (Kieselgel™, 60F254, Art 5744 (manufactured by E. Merck; developing solvent: chloroform/methanol=10/1)