2-methylcyclohexan-1-one

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

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

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: A mixture of 2-methylcyclohexanone (13.1 g), (2R,4R)-2,4-pentanediol (12.2 g), pyridinium p-toluene sulfonate (119 mg) and toluene (120 ml) was refluxed with heating for 8 hours. The reaction mixture was added with a saturated aqueous solution of sodium hydrogen carbonate, extracted with diethyl ether, the organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: hexane/ethyl acetate=100/0 to 0/100 gradient) to obtain 18.0 g of (2R,4R)-2,4,7-trimethyl-1,5-dioxaspiro[5.5]undecane was refluxed with heating for 8 hours extracted with diethyl ether the organic layer was dried over sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel chromatography (elution solvent: hexane/ethyl acetate=100/0 to 0/100 gradient)

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

Procedure: A solution of 2-methylcyclohexanone (11.1 g, 0.099 mol) in chloroform (15 ml) was added during 20 minutes, under nitrogen, to a stirred suspension of m-chloroperbenzoic acid (24.6 g, 0.143 mol) in chloroform (250 ml). After 3 hours, 40 minutes, the mixture was poured into aqueous sodium bicarbonate and extracted with methylene chloride. The extract was washed with brine, dried (MgSO4) and concentrated. The residue was distilled from a small amount of K2CO3 to give 9.58 g, bp 78°-79° C. (2.5-3 mm Hg) of 6-hydroxyheptanoic acid, ε-lactone. extracted with methylene chloride The extract was washed with brine dried (MgSO4) concentrated The residue was distilled from a small amount of K2CO3

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

Procedure: 2-Methylcyclohexanone (170 mg, 1.52 mmol) was mixed with 1-methyl-3,5-dinitro-2-pyridone (296 mg, 1.49 mmol) in 1M methanolic ammonia (30 mL, 30 mmol) and heated at reflux for 3 h. The solvent was evaporated off and the residue was suspended in CHCl3 and flash chromatographed over silica gel (19 g) eluting with EtOAc/hexane (1:10) to afford a white solid (213 mg, 75% yield): mp 61°-63° C. heated at reflux for 3 h The solvent was evaporated off flash chromatographed over silica gel (19 g) eluting with EtOAc/hexane (1:10)

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

Procedure: Using a similar procedure to that described in Example 9-C, N-(5-chloropyridin-2-yl)-2-[(pyrrolidin-3-yloxycarbonyl)amino]benzamide trifluoroacetate (100 mg, 0.211 mmol), 2-methylcyclohexanone (0.12 mL, 1.05 mmol), and sodium cyanoborohydride (53 mg, 0.84 mmol) yielded, after treatment with HCl, 82 mg (80%) of the title compound as the hydrochloride salt. yielded

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

Procedure: Using a similar procedure to that described in Example 9-C, N-(5-chloropyridin-2-yl)-2-[(pyrrolidin-3-yloxycarbonyl)amino]benzamide trifluoroacetate (100 mg, 0.211 mmol), 2-methylcyclohexanone (0.12 mL, 1.05 mmol), and sodium cyanoborohydride (53 mg, 0.84 mmol) yielded, after treatment with HCl, 82 mg (80%) of the title compound as the hydrochloride salt. yielded

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

Procedure: A mixture of 2-methyl-cyclohexanone (112 g, 1.0 mol), aniline (186 g, 2 mol) and ethanol (26 mL) was stirred at room temperature and 12 M hydrochloric acid (167 mL) was added during 30 min. The dark yellow solution was refluxed at 85° C. for seven days. The solution was cooled and diluted with ethyl acetate. The mixture was stirred in an ice bath and made alkaline (pH=9) with a 27% sodium hydroxide solution, keeping the temperature below 30° C. The dark yellow solution was refluxed at 85° C. for seven days The solution was cooled The mixture was stirred in an ice bath the temperature below 30° C.

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

Procedure: A mixture of 2-methyl-cyclohexanone (112 g, 1.0 mol), aniline (186 g, 2 mol) and ethanol (26 mL) was stirred at room temperature and 12 M hydrochloric acid (167 mL) was added during 30 min. The dark yellow solution was refluxed at 85° C. for seven days. The solution was cooled and diluted with ethyl acetate. The mixture was stirred in an ice bath and made alkaline (pH=9) with a 27% sodium hydroxide solution, keeping the temperature below 30° C. The dark yellow solution was refluxed at 85° C. for seven days The solution was cooled The mixture was stirred in an ice bath the temperature below 30° C.

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

Procedure: A solution of 2 ml of NH3 in 50 ml of methanol is charged into a round bottom flask fitted with a gas inlet tube and a mechanical stirrer. Fitted to the gas inlet tube was an oxygen buret graduated in ml and containing oxygen gas. To this solution was added with stirring 0.015 g of CuCl2.H2O and 1.1 g of 2-methyl cyclohexanone. Stirring was continued until all solids had dissolved. A steady stream of oxygen was bubbled into the solution for approximately 20 hours, while the solution was stirred at room temperature. Total oxygen uptake was 190 ml. The methanol solvent was removed by rotary evaporator and the product extracted in ether. The ether layer was concentrated. IR analyses confirmed the presence of the desired compound and the lack of the oxazoline compound. fitted with a gas inlet tube and a mechanical stirrer Fitted to the gas inlet tube To this solution was added had dissolved A steady stream of oxygen was bubbled into the solution for approximately 20 hours, while the solution was stirred at room temperature The methanol solvent was removed by rotary evaporator the product extracted in ether The ether layer was concentrated