3-cyclohexyl-3-oxopropanenitrile

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:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sodium amide (1.87 g) in tetrahydrofuran (1.87 g) was added acetonitrile (2.72 ml) at −50˜−40° C. dropwise and then was added cyclohexanecarboxylic acid methyl ester (2.86 ml) and the mixture was stirred for 1 hour at −20° C. The reaction mixture was poured into cool hydrochloric acid and was extracted with ethyl acetate. The extract was washed with water and a saturated aqueous solution of sodium chloride successively, and was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:1) to give the title compound (0.91 g) having the following physical data. The reaction mixture was poured was extracted with ethyl acetate The extract was washed with water a saturated aqueous solution of sodium chloride successively, and was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:1)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sodium amide (1.87 g) in tetrahydrofuran (1.87 g) was added acetonitrile (2.72 ml) at −50˜−40° C. dropwise and then was added cyclohexanecarboxylic acid methyl ester (2.86 ml) and the mixture was stirred for 1 hour at −20° C. The reaction mixture was poured into cool hydrochloric acid and was extracted with ethyl acetate. The extract was washed with water and a saturated aqueous solution of sodium chloride successively, and was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:1) to give the title compound (0.91 g) having the following physical data. The reaction mixture was poured was extracted with ethyl acetate The extract was washed with water a saturated aqueous solution of sodium chloride successively, and was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:1)

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

Procedure: 60% Sodium hydride (oil suspension) is added to benzene (90 ml) and the mixture is refluxed under heating. Acetonitrile (23 ml) dissolved in benzene (23 ml) is added and the mixture is refluxed for 1 hour. A solution of methyl cyclohexanecarboxylate (63 g) dissolved in benzene (70 ml) is dropwise added and the mixture is refluxed under heating for 5 hours. After the completion of the reaction, the mixture is cooled to room temperature and poured into ice water (200 ml). The organic layer is removed and the aqueous layer is washed with isopropyl ether. The aqueous layer is adjusted to pH 2 with conc. hydrochloric acid and extracted 3 times with isopropyl ether. The extract is dried over anhydrous magnesium sulfate and the solvent is distilled away under reduced pressure to give 34 g of cyanomethyl cyclohexyl ketone. The obtained cyanomethyl cyclohexyl ketone (34 g), morpholine (17.6 ml) and ethyl methyl ketone (18 ml) are dissolved in ethanol (150 ml) and sulfur (6.47 g) is suspended. The suspension is refluxed under heating for 10 hours. After the completion of the reaction, the solvent is distilled away under reduced pressure. the mixture is refluxed under heating is added the mixture is refluxed for 1 hour is dropwise added the mixture is refluxed under heating for 5 hours After the completion of the reaction The organic layer is removed the aqueous layer is washed with isopropyl ether extracted 3 times with isopropyl ether The extract is dried over anhydrous magnesium sulfate the solvent is distilled away under reduced pressure

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

Procedure: To a solution of 3-cyclohexyl-3-oxo-propionitrile in DMF:CS2 (1:1) was added K2CO3 at 0° C. and the reaction mixture stirred at ambient temperature for 2 hours. To the resulting reaction mixture was added chloroacetone (1 equivalent) and the reaction mixture stirred at ambient temperature for 3 hours. Iodomethane was then added and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was partitioned between ethyl acetate and brine, the organic phase dried with MgSO4 and the solvent was removed under reduced pressure. The crude product was purified by silica gel chromatography. To the resulting reaction mixture the reaction mixture stirred at ambient temperature for 3 hours the resulting mixture was stirred at ambient temperature overnight The reaction mixture was partitioned between ethyl acetate and brine the organic phase dried with MgSO4 the solvent was removed under reduced pressure The crude product was purified by silica gel chromatography

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

Procedure: To a solution of 3-cyclohexyl-3-oxo-propionitrile in DMF:CS2 (1:1) was added K2CO3 at 0° C. and the reaction mixture stirred at ambient temperature for 2 hours. To the resulting reaction mixture was added chloroacetone (1 equivalent) and the reaction mixture stirred at ambient temperature for 3 hours. Iodomethane was then added and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was partitioned between ethyl acetate and brine, the organic phase dried with MgSO4 and the solvent was removed under reduced pressure. The crude product was purified by silica gel chromatography. To the resulting reaction mixture the reaction mixture stirred at ambient temperature for 3 hours the resulting mixture was stirred at ambient temperature overnight The reaction mixture was partitioned between ethyl acetate and brine the organic phase dried with MgSO4 the solvent was removed under reduced pressure The crude product was purified by silica gel chromatography

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

Procedure: A solution of 2-cyano-3-cyclohexyl-3-oxo-propionic acid ethyl ester in DMSO:water (10:1) was stirred at 120° C. for 2 hours. The reaction mixture was partitioned between ether and 1N HCl, the organic phase was dried with MgSO4 and the solvent removed under reduced pressure. The reaction mixture was partitioned between ether and 1N HCl the organic phase was dried with MgSO4 the solvent removed under reduced pressure

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

Procedure: A solution of 0.53 mL (10 mmol) of MeCN in 5 ml of THF was cooled in −78° C. bath and 12 mL of 1M LiN(TMS)2 was added. After 5 min, 0.75 mL (5.2 mmol) of methyl cyclohexane carboxylate was added. The cold bath was removed after 1 hr and stirring was continued for another 1 hr. The reaction was acidified with 1.2 N HCl and extracted with ether. The ether layer was washed with brine, dried and concentrated. The residue was chromatographed using a gradient of 10-50% EtOAc-hexane to furnish the desired product. The cold bath was removed after 1 hr was continued for another 1 hr extracted with ether The ether layer was washed with brine dried concentrated The residue was chromatographed

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

Procedure: To a solution of 3-cyclohexyl-3-oxo-propionitrile in DMF:CS2 (1:1) was added K2CO3 at 0° C. and the reaction mixture stirred at ambient temperature for 2 hours. To the resulting reaction mixture was added chloroacetone (1 equivalent) and the reaction mixture stirred at ambient temperature for 3 hours. Iodomethane was then added and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was partitioned between ethyl acetate and brine, the organic phase dried with MgSO4 and the solvent was removed under reduced pressure. The crude product was purified by silica gel chromatography. To the resulting reaction mixture the reaction mixture stirred at ambient temperature for 3 hours the resulting mixture was stirred at ambient temperature overnight The reaction mixture was partitioned between ethyl acetate and brine the organic phase dried with MgSO4 the solvent was removed under reduced pressure The crude product was purified by silica gel chromatography

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

Procedure: A solution of 2-cyano-3-cyclohexyl-3-oxo-propionic acid ethyl ester in DMSO:water (10:1) was stirred at 120° C. for 2 hours. The reaction mixture was partitioned between ether and 1N HCl, the organic phase was dried with MgSO4 and the solvent removed under reduced pressure. The reaction mixture was partitioned between ether and 1N HCl the organic phase was dried with MgSO4 the solvent removed under reduced pressure