methyl 2-(3-oxocyclohexyl)acetate

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

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

Procedure: (3-Oxo-cyclohexyl)-acetic acid methyl ester (240 mg, 1.39 mmol) was dissolved in 5 ml THF and 5 ml ethanol and cooled to 0-5° C. Sodium borohydride (79 mg, 2.09 mmol) was added and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with saturated NaHCO3-solution and extracted three times with ethyl acetate. The organic extracts were washed with brine, dried with sodium sulfate, filtered and evaporated. The crude product (240 mg, 100%) was obtained as a light yellow oil and used without any further purification for the next step. The reaction mixture was quenched with saturated NaHCO3-solution extracted three times with ethyl acetate The organic extracts were washed with brine dried with sodium sulfate filtered evaporated

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

Procedure: rac-cis-(3-Hydroxy-cyclohexyl)-acetic acid methyl ester (500 mg, 2.90 mmol) (Example 5, step 1) was dissolved in 2 ml dichloromethane and tetrapropylammonium perruthenate [TPAP] (102 mg, 0.29 mmol) and 4-methylmorpholine oxide monohydrate (590 mg, 4.35 mmol) were added. The reaction mixture was stirred for 16 hours at room temperature, filtered over dicalite and evaporated to dryness. The residue was purified by flash chromatography on silica gel (heptane/ethyl acetate 100:0→50:50 gradient). The desired compound was obtained as a light yellow liquid (240 mg, 48%). filtered over dicalite evaporated to dryness The residue was purified by flash chromatography on silica gel (heptane/ethyl acetate 100:0→50:50 gradient)

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

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

Procedure: (3-Oxo-cyclohexyl)-acetic acid methyl ester (240 mg, 1.39 mmol) was dissolved in 5 ml THF and 5 ml ethanol and cooled to 0-5° C. Sodium borohydride (79 mg, 2.09 mmol) was added and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with saturated NaHCO3-solution and extracted three times with ethyl acetate. The organic extracts were washed with brine, dried with sodium sulfate, filtered and evaporated. The crude product (240 mg, 100%) was obtained as a light yellow oil and used without any further purification for the next step. The reaction mixture was quenched with saturated NaHCO3-solution extracted three times with ethyl acetate The organic extracts were washed with brine dried with sodium sulfate filtered evaporated

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

Procedure: (3-Oxo-cyclohexyl)-acetic acid methyl ester (240 mg, 1.39 mmol) was dissolved in 5 ml THF and 5 ml ethanol and cooled to 0-5° C. Sodium borohydride (79 mg, 2.09 mmol) was added and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with saturated NaHCO3-solution and extracted three times with ethyl acetate. The organic extracts were washed with brine, dried with sodium sulfate, filtered and evaporated. The crude product (240 mg, 100%) was obtained as a light yellow oil and used without any further purification for the next step. The reaction mixture was quenched with saturated NaHCO3-solution extracted three times with ethyl acetate The organic extracts were washed with brine dried with sodium sulfate filtered evaporated

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

Procedure: rac-cis-(3-Hydroxy-cyclohexyl)-acetic acid methyl ester (500 mg, 2.90 mmol) (Example 5, step 1) was dissolved in 2 ml dichloromethane and tetrapropylammonium perruthenate [TPAP] (102 mg, 0.29 mmol) and 4-methylmorpholine oxide monohydrate (590 mg, 4.35 mmol) were added. The reaction mixture was stirred for 16 hours at room temperature, filtered over dicalite and evaporated to dryness. The residue was purified by flash chromatography on silica gel (heptane/ethyl acetate 100:0→50:50 gradient). The desired compound was obtained as a light yellow liquid (240 mg, 48%). filtered over dicalite evaporated to dryness The residue was purified by flash chromatography on silica gel (heptane/ethyl acetate 100:0→50:50 gradient)

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

Procedure: A solution of 1.3 g of 2-(1-pyrrolyl)-ethylamine, 2.0 g of methyl 3-oxocyclohexylacetate in 150 ml toluene is stirred and refluxed overnight using a Dean Stark water separator. The reaction is cooled and 7 ml glacial acetic acid is added. The solution is stirred and refluxed as before for 6 hours, cooled and the organic solvents are evaporated under reduced pressure. The residue is dissolved in ether and washed with ice cold 1N aqueous sodium hydroxide. The organic layer is separated, dried over magnesium sulfate, and filtered. The ether solution is evaporated under reduced pressure and the residue is crystallized from ether to give 5,6,10,11,12,13-hexahydro-10,13a-methano-13aH-pyrrolo[2',1':3,4]pyrazino[1,2-a]azocin-8(9H)-one, m.p. 130°-132°, the compound of formula II wherein R, R1R2 and R3 represent hydrogen. refluxed overnight The reaction is cooled refluxed as before for 6 hours cooled the organic solvents are evaporated under reduced pressure The residue is dissolved in ether washed with ice cold 1N aqueous sodium hydroxide The organic layer is separated dried over magnesium sulfate filtered The ether solution is evaporated under reduced pressure the residue is crystallized from ether

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

Procedure: (3-Oxo-cyclohexyl)-acetic acid methyl ester (240 mg, 1.39 mmol) was dissolved in 5 ml THF and 5 ml ethanol and cooled to 0-5° C. Sodium borohydride (79 mg, 2.09 mmol) was added and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with saturated NaHCO3-solution and extracted three times with ethyl acetate. The organic extracts were washed with brine, dried with sodium sulfate, filtered and evaporated. The crude product (240 mg, 100%) was obtained as a light yellow oil and used without any further purification for the next step. The reaction mixture was quenched with saturated NaHCO3-solution extracted three times with ethyl acetate The organic extracts were washed with brine dried with sodium sulfate filtered evaporated

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

Procedure: rac-cis-(3-Hydroxy-cyclohexyl)-acetic acid methyl ester (500 mg, 2.90 mmol) (Example 5, step 1) was dissolved in 2 ml dichloromethane and tetrapropylammonium perruthenate [TPAP] (102 mg, 0.29 mmol) and 4-methylmorpholine oxide monohydrate (590 mg, 4.35 mmol) were added. The reaction mixture was stirred for 16 hours at room temperature, filtered over dicalite and evaporated to dryness. The residue was purified by flash chromatography on silica gel (heptane/ethyl acetate 100:0→50:50 gradient). The desired compound was obtained as a light yellow liquid (240 mg, 48%). filtered over dicalite evaporated to dryness The residue was purified by flash chromatography on silica gel (heptane/ethyl acetate 100:0→50:50 gradient)