ethyl butanoate

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:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of ethyl nicotinate (15.1 g, 0.1 mole), ethyl butyrate (17.4 g, 0.15 mole) and sodium ethoxide (10.2 g, 0.15 mole) was stirred and heated under nitrogen at 100°C. for five hours. After cooling, the mixture was diluted with water (150 ml), extracted with diethyl ether (50 ml) and the aqueous layer made acidic to pH1 with concentrated hydrochloric acid (50 ml). The aqueous layer was heated at 90°C. for 2 hours, cooled, and made alkaline with solid potassium carbonate and extracted with diethyl ether (3×75 ml). The dried (magnesium sulphate) organic layer was concentrated and distilled to give propyl 3-pyridyl ketone (b.pt. 118-120°C./14 mm Hg). After cooling extracted with diethyl ether (50 ml) The aqueous layer was heated at 90°C. for 2 hours cooled extracted with diethyl ether (3×75 ml) The dried (magnesium sulphate) organic layer was concentrated distilled

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: 15.6 g of 4,6-dioxononane, prepared from methyl propyl ketone and ethyl butyrate in the presence of lithium amide (according to CA 42 : 4129 f), are dissolved in 160 ml of anhydrous DMF. 4 g of 60% NaH are added in portions. When the exothermic effect has subsided, the mixture is cooled to room temperature and a solution of 27.2 g of 4'-bromomethyl-2-cyanobiphenyl, prepared in Example 4, in 90 ml of DMF is introduced dropwise. The mixture is stirred for 30 min at room temperature and then heated at 60° C. for 2 h. It is concentrated under vacuum and the concentrate is taken up in a water/dichloromethane mixture and acidified with a dilute solution of HCl. After decantation, the aqueous phase is extracted twice with dichloromethane. The organic phases are washed with water, dried and then concentrated to give 36.3 g of an oil, which is purified by chromatography twice in succession (eluent: chloroform, then cyclohexane 90%/ethyl acetate 10% respectively) to give a solid identified by NMR as being the enol tautomer melting at 105° C., and an oil corresponding to the diketone tautomeric form. is introduced dropwise heated at 60° C. for 2 h It is concentrated under vacuum After decantation, the aqueous phase is extracted twice with dichloromethane The organic phases are washed with water dried concentrated

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

Procedure: 15.6 g of 4,6-dioxononane, prepared from methyl propyl ketone and ethyl butyrate in the presence of lithium amide (according to CA 42 : 4129 f), are dissolved in 160 ml of anhydrous DMF. 4 g of 60% NaH are added in portions. When the exothermic effect has subsided, the mixture is cooled to room temperature and a solution of 27.2 g of 4'-bromomethyl-2-cyanobiphenyl, prepared in Example 4, in 90 ml of DMF is introduced dropwise. The mixture is stirred for 30 min at room temperature and then heated at 60° C. for 2 h. It is concentrated under vacuum and the concentrate is taken up in a water/dichloromethane mixture and acidified with a dilute solution of HCl. After decantation, the aqueous phase is extracted twice with dichloromethane. The organic phases are washed with water, dried and then concentrated to give 36.3 g of an oil, which is purified by chromatography twice in succession (eluent: chloroform, then cyclohexane 90%/ethyl acetate 10% respectively) to give a solid identified by NMR as being the enol tautomer melting at 105° C., and an oil corresponding to the diketone tautomeric form. is introduced dropwise heated at 60° C. for 2 h It is concentrated under vacuum After decantation, the aqueous phase is extracted twice with dichloromethane The organic phases are washed with water dried concentrated

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

Procedure: 15.6 g of 4,6-dioxononane, prepared from methyl propyl ketone and ethyl butyrate in the presence of lithium amide (according to CA 42: 4129 f), are dissolved in 160 ml of anhydrous DMF. 4 g of 60% NaH are added in portions. When the exothermic effect has subsided, the mixture is cooled to room temperature and a solution of 27.2 g of 4'-bromomethyl-2-cyanobiphenyl, prepared in Example 4, in 90 ml of DMF is introduced dropwise. The mixture is stirred for 30 min at room temperature and then heated at 60° C. for 2 h. It is concentrated under vacuum and the concentrate is taken up in a water/dichloromethane mixture and acidified with a dilute solution of HCl. After decantation, the aqueous phase is extracted twice with dichloromethane. The organic phases are washed with water, dried and then concentrated to give 36.3 g of an oil, which is purified by chromatography twice in succession (eluent: chloroform, then cyclohexane 90%/ethyl acetate 10% respectively) to give a solid identified by NMR as being the enol tautomer melting at 105° C., and an oil corresponding to the diketone tautomeric form. is introduced dropwise heated at 60° C. for 2 h It is concentrated under vacuum After decantation, the aqueous phase is extracted twice with dichloromethane The organic phases are washed with water dried concentrated

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

Procedure: 15.6 g of 4,6-dioxononane, prepared from methyl propyl ketone and ethyl butyrate in the presence of lithium amide (according to CA 42: 4129 f), are dissolved in 160 ml of anhydrous DMF. 4 g of 60% NaH are added in portions. When the exothermic effect has subsided, the mixture is cooled to room temperature and a solution of 27.2 g of 4'-bromomethyl-2-cyanobiphenyl, prepared in Example 4, in 90 ml of DMF is introduced dropwise. The mixture is stirred for 30 min at room temperature and then heated at 60° C. for 2 h. It is concentrated under vacuum and the concentrate is taken up in a water/dichloromethane mixture and acidified with a dilute solution of HCl. After decantation, the aqueous phase is extracted twice with dichloromethane. The organic phases are washed with water, dried and then concentrated to give 36.3 g of an oil, which is purified by chromatography twice in succession (eluent: chloroform, then cyclohexane 90%/ethyl acetate 10% respectively) to give a solid identified by NMR as being the enol tautomer melting at 105° C., and an oil corresponding to the diketone tautomeric form. is introduced dropwise heated at 60° C. for 2 h It is concentrated under vacuum After decantation, the aqueous phase is extracted twice with dichloromethane The organic phases are washed with water dried concentrated

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

Procedure: The title compound was prepared from butyric acid ethyl ester and ethyl formate employing the procedure set forth in Step 1 of Example 87.