4-ethyl-3-oxohexanenitrile

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 4-ethyl-3-oxo-hexanenitrile (1.013 g, 7.28 mmol), acetic anhydride (1.5 ml) and triethyl orthoacetate (1.240 g, 7.64 mmol) was heated to reflux overnight. The reaction mixture was taken up in ethyl acetate and water. The brine and the ethyl acetate layer were separated. The organic layer was dried and concentrated to give 1.262 g of dry oil which was used directly for the next reaction. 1H NMR (CDCl3): 0.8-1.0(m,6H), 1.44(t,3H), 1.4-1.8(m,4H), 2.61(s,3H), 3.03(m,1H), 4.28(q, 2H)ppm. was heated to reflux overnight The brine and the ethyl acetate layer were separated The organic layer was dried concentrated

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

Procedure: A mixture of 4-ethyl-3-oxo-hexanenitrile (1.013 g, 7.28 mmol), acetic anhydride (1.5 ml) and triethyl orthoacetate (1.240 g, 7.64 mmol) was heated to reflux overnight. The reaction mixture was taken up in ethyl acetate and water. The brine and the ethyl acetate layer were separated. The organic layer was dried and concentrated to give 1.262 g of dry oil which was used directly for the next reaction. 1H NMR (CDCl3): 0.8-1.0(m,6H), 1.44(t,3H), 1.4-1.8(m,4H), 2.61(s,3H), 3.03(m,1H), 4.28(q, 2H)ppm. was heated to reflux overnight The brine and the ethyl acetate layer were separated The organic layer was dried concentrated

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

Procedure: A mixture of 4-ethyl-3-oxo-hexanenitrile (1.013 g, 7.28 mmol), acetic anhydride (1.5 ml) and triethyl orthoacetate (1.240 g, 7.64 mmol) was heated to reflux overnight. The reaction mixture was taken up in ethyl acetate and water. The brine and the ethyl acetate layer were separated. The organic layer was dried and concentrated to give 1.262 g of dry oil which was used directly for the next reaction. 1H NMR (CDCl3): 0.8-1.0(m,6H), 1.44(t,3H), 1.4-1.8(m,4H), 2.61(s,3H), 3.03(m,1H), 4.28(q, 2H)ppm. was heated to reflux overnight The brine and the ethyl acetate layer were separated The organic layer was dried concentrated

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

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

Procedure: 13.1 g (94 mmol) of 1-Cyano-3-ethyl-2-oxo-pentane were dissolved in toluene and 15 g (194 mmol) ammonium acetate and 1 ml dry acetic acid were added. The mixture was reflured 2 h and then cooled to room temperature. The mixture was washed, dried and concentrated. Perification by customary methods gove 13. 1 g (100% of theory) of the title compound as a oil. The mixture was washed dried concentrated

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

Procedure: The title compound was prepared in analogy to example 101 step B from (2-amino-5-chloro-phenyl)-(2-methyl-pyridin-4-yl)-methanone (prepared in analogy to example 126 step B) and 4-ethyl-3-oxo-hexanenitrile (prepared as described in example 101 step A). Yellow solid. MS (ESI): 350.5 (M+H)+.

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

Procedure: The title compound was prepared in analogy to example 101 step B from (2-amino-4-methoxy-phenyl)-phenyl-methanone and 4-ethyl-3-oxo-hexanenitrile (prepared as described in example 101 step A). Colorless oil. MS (ESI): 331.4 (M+H)+.

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

Procedure: The title compound was prepared in analogy to example 101 step B from (2-amino-5-trifluoromethyl-phenyl)-phenyl-methanone and 4-ethyl-3-oxo-hexanenitrile (prepared as described in example 101 step A). Off-white solid. MS (ESI): 369.4 (M+H)+.

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

Procedure: The title compound was prepared in analogy to example 101 step B from (2-amino-5-chloro-phenyl)-(3-chloro-phenyl)-methanone (prepared as described in example 91 step A) and 4-ethyl-3-oxo-hexanenitrile (prepared as described in example 101 step A). Light yellow oil. MS (ESI): 369.3 (M+H)+.

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

Procedure: The title compound was prepared in analogy to example 101 step B from (2-amino-5-chloro-4-fluoro-phenyl)-phenyl-methanone (prepared as described in example 105 step D) and 4-ethyl-3-oxo-hexanenitrile (prepared as described in example 101 step A). Off-white solid. MS (ESI): 353.4 (M+H)+.

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

Procedure: A solution of (2-amino-5-chlorophenyl)(phenyl)methanone (700 mg, 3.02 mmol), 4-ethyl-3-oxo-hexanenitrile (505 mg, 3.63 mmol) and methanesulfonic acid (290 mg, 196 μl, 3.02 mmol) in toluene (40 ml) was stirred for 5 min at room temperature and then heated to reflux using a Dean-Stark-trap to remove water. After 2.5 h the mixture was cooled to room temperature, washed with saturated NaHCO3 solution and water and was evaporated. n-Heptane was added to the remaining residue and the off-white precipitate that formed was filtered off. The precipitate was again dissolved in EtOAc and the solution was washed with saturated NaHCO3 solution and water and was evaporated to yield the title compound (461 mg, 46%) as yellow solid. The filtrate was concentrated and the remaining residue was purified by column chromatography (silica gel, heptane/EtOAc 100:0-0:100) to afford a second batch of the title compound (347 mg, 34%) as yellow solid. MS (ESI): 335.1 (M+H)+. heated to reflux to remove water washed with saturated NaHCO3 solution and water was evaporated n-Heptane was added to the remaining residue the off-white precipitate that formed was filtered off The precipitate was again dissolved in EtOAc the solution was washed with saturated NaHCO3 solution and water was evaporated