tert-butyl 3-oxocyclopentane-1-carboxylate

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

Procedure: To a solution of tert-butyl 3-oxocyclopentanecarboxylate (19.8 g, 107 mmol) in 1:1 DCM/methanol (150 mL) was added trimethylorthoformate (46.8 mL, 428 mmol), followed by TsOH.H2O (˜0.5 g). The reaction mixture was stirred at rt for 2 h. Then more TsOH.H2O (˜0.25 g) was added and the reaction mixture was stirred overnight. The reaction mixture was concentrated at rt and the resulting residue was dissolved in ether and washed with saturated NaHCO3 solution, then with brine. The ethereal layer was dried over anhydrous MgSO4, filtered, and concentrated. Purification by flash chromatography (silica, 15% ethyl acetate/hexane) gave tert-butyl 3,3-dimethoxycyclopentanecarboxylate. 1H NMR (500 MHz, CDCl3): 3.21 (s, 3H), 3.20 (s, 3H), 2.80 (m, 1H), 2.10 to 1.80 (bm, 6H), 1.46 (s, 9H). 13C NMR (125 MHz, CDCl3): 174.9, 111.2, 80.3, 67.8, 49.2, 42.5, 37.4, 33.8, 28.3, 22.0. the reaction mixture was stirred overnight The reaction mixture was concentrated at rt the resulting residue was dissolved in ether washed with saturated NaHCO3 solution The ethereal layer was dried over anhydrous MgSO4 filtered concentrated Purification by flash chromatography (silica, 15% ethyl acetate/hexane)

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

Procedure: To a solution of tert-butyl 3-oxocyclopentanecarboxylate (19.8 g, 107 mmol) in 1:1 DCM/methanol (150 mL) was added trimethylorthoformate (46.8 mL, 428 mmol), followed by TsOH.H2O (˜0.5 g). The reaction mixture was stirred at rt for 2 h. Then more TsOH.H2O (˜0.25 g) was added and the reaction mixture was stirred overnight. The reaction mixture was concentrated at rt and the resulting residue was dissolved in ether and washed with saturated NaHCO3 solution, then with brine. The ethereal layer was dried over anhydrous MgSO4, filtered, and concentrated. Purification by flash chromatography (silica, 15% ethyl acetate/hexane) gave tert-butyl 3,3-dimethoxycyclopentanecarboxylate. 1H NMR (500 MHz, CDCl3): 3.21 (s, 3H), 3.20 (s, 3H), 2.80 (m, 1H), 2.10 to 1.80 (bm, 6H), 1.46 (s, 9H). 13C NMR (125 MHz, CDCl3): 174.9, 111.2, 80.3, 67.8, 49.2, 42.5, 37.4, 33.8, 28.3, 22.0. the reaction mixture was stirred overnight The reaction mixture was concentrated at rt the resulting residue was dissolved in ether washed with saturated NaHCO3 solution The ethereal layer was dried over anhydrous MgSO4 filtered concentrated Purification by flash chromatography (silica, 15% ethyl acetate/hexane)

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

Procedure: To a solution of tert-butyl 3-oxocyclopentanecarboxylate (19.8 g, 107 mmol) in 1:1 DCM/methanol (150 mL) was added trimethylorthoformate (46.8 mL, 428 mmol), followed by TsOH.H2O (˜0.5 g). The reaction mixture was stirred at room temperature for 2 h. Then more TsOH.H2O (˜0.25 g) was added and the reaction mixture was stirred overnight. The reaction mixture was concentrated at room temperature and the resulting residue was dissolved in ether and washed with saturated NaHCO3 solution, then with brine. The ethereal layer was dried over anhydrous MgSO4, filtered, and concentrated. Purification by flash chromatography (silica, 15% ethyl acetate/hexane) gave 22.2 g (90%) of tert-butyl 3,3-dimethoxycyclopentanecarboxylate. 1H NMR (500 MHz, CDCl3): 3.21 (s, 3H), 3.20 (s, 3H), 2.80 (m, 1H), 2.10 to 1.80 (bm, 6H), 1.46 (s, 9H). 13C NMR (125 MHz, CDCl3): 174.9, 111.2, 80.3, 67.8, 49.2, 42.5, 37.4, 33.8, 28.3, 22.0. the reaction mixture was stirred overnight The reaction mixture was concentrated at room temperature the resulting residue was dissolved in ether washed with saturated NaHCO3 solution The ethereal layer was dried over anhydrous MgSO4 filtered concentrated Purification by flash chromatography (silica, 15% ethyl acetate/hexane)

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

Procedure: To a solution of tert-butyl 3-oxocyclopentanecarboxylate (19.8 g, 107 mmol) in 1:1 DCM/methanol (150 mL) was added trimethylorthoformate (46.8 mL, 428 mmol), followed by TsOH.H2O (˜0.5 g). The reaction mixture was stirred at room temperature for 2 h. Then more TsOH.H2O (˜0.25 g) was added and the reaction mixture was stirred overnight. The reaction mixture was concentrated at room temperature and the resulting residue was dissolved in ether and washed with saturated NaHCO3 solution, then with brine. The ethereal layer was dried over anhydrous MgSO4, filtered, and concentrated. Purification by flash chromatography (silica, 15% ethyl acetate/hexane) gave 22.2 g (90%) of tert-butyl 3,3-dimethoxycyclopentanecarboxylate. 1H NMR (500 MHz, CDCl3): 3.21 (s, 3H), 3.20 (s, 3H), 2.80 (m, 1H), 2.10 to 1.80 (bm, 6H), 1.46 (s, 9H). 13C NMR (125 MHz, CDCl3): 174.9, 111.2, 80.3, 67.8, 49.2, 42.5, 37.4, 33.8, 28.3, 22.0. the reaction mixture was stirred overnight The reaction mixture was concentrated at room temperature the resulting residue was dissolved in ether washed with saturated NaHCO3 solution The ethereal layer was dried over anhydrous MgSO4 filtered concentrated Purification by flash chromatography (silica, 15% ethyl acetate/hexane)

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

Procedure: To a solution of tert-butyl 3-oxocyclopentanecarboxylate (19.8 g, 107 mmol) in 1:1 DCM/methanol (150 mL) was added trimethylorthoformate (46.8 mL, 428 mmol), followed by TsOH.H2O (˜0.5 g). The reaction mixture was stirred at room temperature for 2 h. Then more TsOH.H2O (˜0.25 g) was added and the reaction mixture was stirred overnight. The reaction mixture was concentrated at room temperature and the resulting residue was dissolved in ether and washed with saturated NaHCO3 solution, then with brine. The ethereal layer was dried over anhydrous MgSO4, filtered, and concentrated. Purification by flash chromatography (silica, 15% ethyl acetate/hexane) gave 22.2 g (90%) of tert-butyl 3,3-dimethoxycyclopentanecarboxylate. the reaction mixture was stirred overnight The reaction mixture was concentrated at room temperature the resulting residue was dissolved in ether washed with saturated NaHCO3 solution The ethereal layer was dried over anhydrous MgSO4 filtered concentrated Purification by flash chromatography (silica, 15% ethyl acetate/hexane)

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cold (ice bath) solution of Rac-3-Oxo-cyclopentanecarboxylic acid tert-butyl ester (1.43 g) in methanol (9 mL) was added sodium borohydride (0.293 g). The mixture was stirred 25 min at 0-5° C. then concentrated in vacuo. Ethyl acetate was added to the residue and the mixture was washed with water, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with dichloromethane/methanol (19:1 v/v) as eluant to afford the title compound (0.963 g, 67%) as colorless oil. MS (EI): 187.1 (M+H)+. then concentrated in vacuo Ethyl acetate was added to the residue the mixture was washed with water dried over sodium sulfate concentrated in vacuo The residue was purified by flash chromatography on silica gel with dichloromethane/methanol (19:1 v/v) as eluant

Conditions: temp:2.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cold (ice bath) solution of 3-oxo-1-cyclopentanecarboxylic acid (1.50 g), tert-butylalcohol (1.05 g) and 4-dimethylaminopyridine (140 mg) in dichloromethane (9 mL) was added a solution of dicyclocarbodiimide in dichloromethane (9 mL). The mixture was stirred 3 hours at ca. 2° C. then diethylether (30 mL) was added and the precipitate was filtered off and discarded. The solution was concentrated in vacuo. The residue was purified by flash chromatography on silica gel with cyclohexane/ethyl acetate (9:1 v/v) as eluant to afford the title compound (1.80 g, 96%) as colorless oil. MS (EI): 111 (M-OtBu.)+. the precipitate was filtered off The solution was concentrated in vacuo The residue was purified by flash chromatography on silica gel with cyclohexane/ethyl acetate (9:1 v/v) as eluant

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

Procedure: To a solution of tert-butyl 3-oxocyclopentanecarboxylate (19.8 g, 107 mmol) in 1:1 DCM/methanol (150 mL) was added trimethylorthoformate (46.8 mL, 428 mmol), followed by TsOH.H2O (˜0.5 g). The reaction mixture was stirred at rt for 2 h. Then more TsOH.H2O (˜0.25 g) was added and the reaction mixture was stirred overnight. The reaction mixture was concentrated at rt and the resulting residue was dissolved in ether and washed with saturated NaHCO3 solution, then with brine. The ethereal layer was dried over anhydrous MgSO4, filtered, and concentrated. Purification by flash chromatography (silica, 15% ethyl acetate/hexane) gave tert-butyl 3,3-dimethoxycyclopentanecarboxylate. 1H NMR (500 MHz, CDCl3): 3.21 (s, 3H), 3.20 (s, 3H), 2.80 (m, 1H), 2.10 to 1.80 (bm, 6H), 1.46 (s, 9H). 13C NMR (125 MHz, CDCl3): 174.9, 111.2, 80.3, 67.8, 49.2, 42.5, 37.4, 33.8, 28.3, 22.0. the reaction mixture was stirred overnight The reaction mixture was concentrated at rt the resulting residue was dissolved in ether washed with saturated NaHCO3 solution The ethereal layer was dried over anhydrous MgSO4 filtered concentrated Purification by flash chromatography (silica, 15% ethyl acetate/hexane)