methyl 3-oxocyclohexane-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-oxo-1-cyclohexanecarboxylic acid methyl ester (1.1 g, 7.04 mmol) was dissolved in methanol (25 ml) and cooled to 0° C. under N2. Sodium borohydride (0.550 g, 14.54 mmol) was added in portions and the resulting solution stirred at 0° C. for 2 h. The solution was then diluted by the dropwise addition of water, followed by EtOAc (100 mL). The aqueous phase was separated and extracted with EtOAc (2×50 ml). The combined organic layers were washed with brine, dried over sodium sulphate, and concentrated in vacuo to give the title compound. TLC: 40% EtOAc/hexanes, high Rf: 0.4, low Rf: 0.3. The aqueous phase was separated extracted with EtOAc (2×50 ml) The combined organic layers were washed with brine dried over sodium sulphate concentrated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of trimethylsilyltrifluoromethanesulfonate (0.034 mL) in dry dichloromethane (5 mL) was added 1,2-bis(trimethylsiloxy)ethane (4.55 mL) followed by methyl 3-oxocyclohexanecarboxylate (2.9 g). The reaction mixture was stirred for 3 hours at −78° C. The reaction mixture was quenched with dry pyridine (0.5 mL), poured into saturated aqueous NaHCO3, and extracted with ether. The ether layer was dried over Na2CO3/Na2SO4. The reaction mixture was concentrated and purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes to provide the title compound. The reaction mixture was quenched with dry pyridine (0.5 mL) poured into saturated aqueous NaHCO3 extracted with ether The ether layer was dried over Na2CO3/Na2SO4 The reaction mixture was concentrated purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of trimethylsilyltrifluoromethanesulfonate (0.034 mL) in dry dichloromethane (5 mL) was added 1,2-bis(trimethylsiloxy)ethane (4.55 mL) followed by methyl 3-oxocyclohexanecarboxylate (2.9 g). The reaction mixture was stirred for 3 hours at −78° C. The reaction mixture was quenched with dry pyridine (0.5 mL), poured into saturated aqueous NaHCO3, and extracted with ether. The ether layer was dried over Na2CO3/Na2SO4. The reaction mixture was concentrated and purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes to provide the title compound. The reaction mixture was quenched with dry pyridine (0.5 mL) poured into saturated aqueous NaHCO3 extracted with ether The ether layer was dried over Na2CO3/Na2SO4 The reaction mixture was concentrated purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes

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

Procedure: To a solution of trimethylsulfoxonium iodide (53.3 g, 242 mmol) in dry DMSO (300 mL) under N2, was added sodium hydride (9.69 g, 242 mmol) portionwise over 30 min. This light yellow mixture was stirred at RT for 1 h. The reaction mixture was then cooled in an ice bath and treated with methyl 3-oxocyclohexanecarboxylate (29.0 g, 186 mmol) dropwise while maintaining a temperature at or below 27° C. The resulting reaction mixture was allowed to warm slowly to RT and stir overnight. The reaction was diluted with water and extracted with DCM. The combined organics were washed with water, dried over MgSO4, filtered, and concentrated to provide methyl 1-oxaspiro[2.5]octane-5-carboxylate (31.8 g, 85% yield) which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 3.66 (s, 3H), 2.71 (m, 1H), 2.65 (d, J=1.76 Hz, 2H), 2.00 (dd J=11.8, 13.6 Hz, 2H), 1.74-1.85 (m, 2H), 1.60-1.74 (m, 1H), 1.40-1.56 (m, 2H), 1.17-1.32 (m, 1H). The reaction mixture was then cooled in an ice bath while maintaining a temperature at or below 27° C The resulting reaction mixture to warm slowly to RT stir overnight extracted with DCM The combined organics were washed with water dried over MgSO4 filtered concentrated

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

Procedure: To a solution of trimethylsulfoxonium iodide (53.3 g, 242 mmol) in dry DMSO (300 mL) under N2, was added sodium hydride (9.69 g, 242 mmol) portionwise over 30 min. This light yellow mixture was stirred at RT for 1 h. The reaction mixture was then cooled in an ice bath and treated with methyl 3-oxocyclohexanecarboxylate (29.0 g, 186 mmol) dropwise while maintaining a temperature at or below 27° C. The resulting reaction mixture was allowed to warm slowly to RT and stir overnight. The reaction was diluted with water and extracted with DCM. The combined organics were washed with water, dried over MgSO4, filtered, and concentrated to provide methyl 1-oxaspiro[2.5]octane-5-carboxylate (31.8 g, 85% yield) which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 3.66 (s, 3H), 2.71 (m, 1H), 2.65 (d, J=1.76 Hz, 2H), 2.00 (dd J=11.8, 13.6 Hz, 2H), 1.74-1.85 (m, 2H), 1.60-1.74 (m, 1H), 1.40-1.56 (m, 2H), 1.17-1.32 (m, 1H). The reaction mixture was then cooled in an ice bath while maintaining a temperature at or below 27° C The resulting reaction mixture to warm slowly to RT stir overnight extracted with DCM The combined organics were washed with water dried over MgSO4 filtered concentrated

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

Procedure: Ruthenium (IV) oxide hydrate (1.47 g, 11.1 mmol) and sodium bromate (100 g, 664 mmol) were combined in diethyl ether (600 mL) and water (300 mL). The resulting black mixture was stirred for 10 min and then cooled in an ice bath. Methyl 3-hydroxycyclohexanecarboxylate (35 g, 221 mmol) was dissolved in ether (to bring total volume to 100 mL) and was added dropwise to the ice cold reaction mixture. The temperature was not allowed to go above 30° C. The reaction mixture was stirred for 1 h with the reaction temperature at ˜15° C. Isopropanol was carefully added to the reaction mixture at a rate necessary to keep the reaction temperature at ˜27° C. The layers were separated and the organic layers were washed with ether. The combined organics were washed with saturated aqueous NaHCO3 solution and brine. The organics were then dried over MgSO4, filtered, and concentrated to provide methyl 3-oxocyclohexanecarboxylate (34.5 g, 100% yield) which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 3.68 (s, 3H), 2.79 (m, 1H), 2.52 (d, J=7.78 Hz, 2H), 2.23-2.42 (m, 2H), 1.98-2.15 (m, 2H), 1.82 (d, J=10.29 Hz, 1H), 1.61-1.77 (m, 1H). cooled in an ice bath to go above 30° C The reaction mixture was stirred for 1 h with the reaction temperature at ˜15° C at ˜27° C The layers were separated the organic layers were washed with ether The combined organics were washed with saturated aqueous NaHCO3 solution and brine The organics were then dried over MgSO4 filtered concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of trimethylsilyltrifluoromethanesulfonate (0.034 mL) in dry dichloromethane (5 mL) was added 1,2-bis(trimethylsiloxy)ethane (4.55 mL) followed by methyl 3-oxocyclohexanecarboxylate (2.9 g). The reaction mixture was stirred for 3 hours at −78° C. The reaction mixture was quenched with dry pyridine (0.5 mL), poured into saturated aqueous NaHCO3, and extracted with ether. The ether layer was dried over Na2CO3/Na2SO4. The reaction mixture was concentrated and purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes to provide the title compound. The reaction mixture was quenched with dry pyridine (0.5 mL) poured into saturated aqueous NaHCO3 extracted with ether The ether layer was dried over Na2CO3/Na2SO4 The reaction mixture was concentrated purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes

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

Procedure: Methyl 3-oxocyclohexanecarboxylate (930 mg) and pyridinium p-toluenesulfonate (299 mg) were combined in toluene (29.8 mL) to give a colorless solution. Ethylene glycol (0.996 mL) was added and the reaction was refluxed under Dean-Stark conditions for 2 days. The reaction was cooled to room temperature, triethylamine was added, and then the mixture was concentrated by rotary evaporation. The residue was purified by regular phase flash column chromatography (Analogix 0-40% hexane/ethyl acetate). to give a colorless solution the reaction was refluxed under Dean-Stark conditions for 2 days the mixture was concentrated by rotary evaporation The residue was purified by regular phase flash column chromatography (Analogix 0-40% hexane/ethyl acetate)

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

Procedure: Methyl 3-oxocyclohexanecarboxylate (930 mg) and pyridinium p-toluenesulfonate (299 mg) were combined in toluene (29.8 mL) to give a colorless solution. Ethylene glycol (0.996 mL) was added and the reaction was refluxed under Dean-Stark conditions for 2 days. The reaction was cooled to room temperature, triethylamine was added, and then the mixture was concentrated by rotary evaporation. The residue was purified by regular phase flash column chromatography (Analogix 0-40% hexane/ethyl acetate). to give a colorless solution the reaction was refluxed under Dean-Stark conditions for 2 days the mixture was concentrated by rotary evaporation The residue was purified by regular phase flash column chromatography (Analogix 0-40% hexane/ethyl acetate)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of trimethylsilyltrifluoromethanesulfonate (0.034 mL) in dry dichloromethane (5 mL) was added 1,2-bis(trimethylsiloxy)ethane (4.55 mL) followed by methyl 3-oxocyclohexanecarboxylate (2.9 g). The reaction mixture was stirred for 3 hours at −78° C. The reaction mixture was quenched with dry pyridine (0.5 mL), poured into saturated aqueous NaHCO3, and extracted with ether. The ether layer was dried over Na2CO3/Na2SO4. The reaction mixture was concentrated and purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes to provide the title compound. The reaction mixture was quenched with dry pyridine (0.5 mL) poured into saturated aqueous NaHCO3 extracted with ether The ether layer was dried over Na2CO3/Na2SO4 The reaction mixture was concentrated purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of trimethylsilyltrifluoromethanesulfonate (0.034 mL) in dry dichloromethane (5 mL) was added 1,2-bis(trimethylsiloxy)ethane (4.55 mL) followed by methyl 3-oxocyclohexanecarboxylate (2.9 g). The reaction mixture was stirred for 3 hours at −78° C. The reaction mixture was quenched with dry pyridine (0.5 mL), poured into saturated aqueous NaHCO3, and extracted with ether. The ether layer was dried over Na2CO3/Na2SO4. The reaction mixture was concentrated and purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes to provide the title compound. The reaction mixture was quenched with dry pyridine (0.5 mL) poured into saturated aqueous NaHCO3 extracted with ether The ether layer was dried over Na2CO3/Na2SO4 The reaction mixture was concentrated purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes