methyl 4-hydroxy-1-methylcyclohexane-1-carboxylate

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

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

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

Procedure: To a solution of 3.7 g (20.1 mmol) of 1-methyl-4-oxocyclohexanecarboxylic acid methyl ester in mixture of methanol and ethanol (6 mL+15 mL) was added 200 mg (5.29 mmol) of sodium borohydride at 0° C., and stirred for 1 hour at 0° C. After addition of water thereto, the reaction mixture was concentrated under a reduced pressure and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated brine successively and dried over anhydrous magnesium sulfate. Upon removal of the solvent by evaporation, 3.8 g (yield 100%) of 4-hydroxy-1-methylcyclohexanecarboxylic acid methyl ester was obtained as colorless liquid. Its physical property is shown below. the reaction mixture was concentrated under a reduced pressure the residue was extracted with ethyl acetate The organic layer was washed with water and saturated brine successively dried over anhydrous magnesium sulfate Upon removal of the solvent by evaporation

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

Procedure: To a solution of methyl 4-hydroxy-1-methylcyclohexane-1-carboxylate (2.1 g, 12.19 mmol, 1.00 equiv) in 20 mL of dichloromethane was added DIEA (4.74 g, 36.68 mmol, 3.01 equiv) and SEMCl (4.08 g, 24.47 mmol, 2.00 equiv) at 0° C. under nitrogen. The resulting solution was stirred for 2 h at room temperature and quenched with water. The resulting solution was extracted with 3×100 mL of ethyl acetate. The organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/20) to give the desired methyl 1-methyl-4-[[2-(trimethylsilyl)ethoxy]methoxy]cyclohexane-1-carboxylate (3.6 g, 98%) as a colorless oil. quenched with water The resulting solution was extracted with 3×100 mL of ethyl acetate The organic layers were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

Procedure: Into a 250-mL round-bottom flask containing a solution of 4-(methoxycarbonyl)-4-methylcyclohexyl 4-nitrobenzoate (4.5 g, 14.00 mmol, 1.00 equiv) in methanol/water (30 mL/6 mL) was added potassium carbonate (5.8 g, 41.97 mmol, 3.00 equiv) and the resulting solution was stirred overnight at 50° C. The reaction was quenched by the addition of NH4Cl (aq.) and extracted with 3×100 mL of ethyl acetate. The organic phase was washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/2) to afford the desired methyl 4-hydroxy-1-methylcyclohexane-1-carboxylate (2.2 g, 91%) as a colorless oil. The reaction was quenched by the addition of NH4Cl (aq.) extracted with 3×100 mL of ethyl acetate The organic phase was washed with brine dried over sodium sulfate concentrated under vacuum

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

Procedure: To a solution of methyl 4-hydroxy-1-methylcyclohexane-1-carboxylate (5.8 g, 33.68 mmol, 1.00 equiv) and 4-nitrobenzoic acid (11.26 g, 67.38 mmol, 2.00 equiv) in 80 mL of anhydrous THF was added PPh3 (17.67 g, 67.37 mmol, 2.00 equiv) at room temperature. Then DIAD (13.62 g, 67.36 mmol, 2.00 equiv) was added dropwise and the resulting solution was stirred for 2 h at room temperature. The reaction was quenched water, extracted with 3×150 mL of ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/50) to give 4-(methoxycarbonyl)-4-methylcyclohexyl 4-nitrobenzoate (5.5 g, 51%) as a white solid. The reaction was quenched water extracted with 3×150 mL of ethyl acetate The combined organic layers were dried over sodium sulfate concentrated under vacuum

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

Procedure: To a solution of methyl 4-[(tert-butyldimethylsilyl)oxy]-1-methylcyclohexane-1-carboxylate (10.0 g, 34.91 mmol, 1.00 equiv) in 100 mL of tetrahydrofuran was added TBAF-3H2O (16.5 g, 52.30 mmol, 1.50 equiv) at room temperature and stirred for 5 h. Then the reaction was quenched with water, extracted with 3×100 mL of ethyl acetate. The organic layers were combined, washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/2) to give 5.8 g (96%) of methyl 4-hydroxy-1-methylcyclohexane-1-carboxylate as a light yellow oil. Then the reaction was quenched with water extracted with 3×100 mL of ethyl acetate washed with brine dried over sodium sulfate concentrated under vacuum