propan-2-yl 4-chloro-3-oxobutanoate

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

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

Procedure: 2-Methyl-1-(2-hydroxyethyl)-imidazo[4,5-c]pyridine (5 g, 28.5 mmole) was added to a suspension of sodium hydride (60% oil dispersion, 2.3 g, 57 mmole) in dry tetrahydrofuran (100 ml) and the mixture was sonicated for 2 hours at room temperature. A solution of isopropyl 4-chloroacetoacetate (5.1 g, 28.5 mmole) in tetrahydrofuran (100 ml) was added dropwise under nitrogen with sonication and the mixture was sonicated for 5 hours at room temperature. 2N Hydrochloric acid (100 ml) was added and the tetrahydrofuran removed under reduced pressure. The aqueous solution was washed with methylene chloride (2×50 ml), neutralised with potassium carbonate and extracted with ethyl acetate (3×25 ml). The combined extracts were washed with water, dried over magnesium sulphate and evaporated. The residue was chromatographed on silica, eluting with ethyl acetate containing 10% isopropyl alcohol to yield isopropyl 4-[2-(2-methyl-1-imidazo[4,5-c]pyridyl)ethoxy]-3-ketobutanoate (5.3 g, 58%). Rf (silica; methanol, ethyl acetate 1:4) 0.13; N.M.R. (CDCl3) δ=1.05 (d, J=6 Hz, 6H); 2.50 (s, 3H); 3.15 (s, 2H); 3.67 (t, J=5.5 Hz, 2H); 3.93 (s, 2H); 4.19 (t, J=5.5 Hz, 2H); 4.8 (m, 1H); 7.11-8.19 (m, 3H). the mixture was sonicated for 2 hours at room temperature the mixture was sonicated for 5 hours at room temperature the tetrahydrofuran removed under reduced pressure The aqueous solution was washed with methylene chloride (2×50 ml) extracted with ethyl acetate (3×25 ml) The combined extracts were washed with water dried over magnesium sulphate evaporated The residue was chromatographed on silica eluting with ethyl acetate containing 10% isopropyl alcohol

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

Procedure: Sodium benzylate in tetrahydrofuran was reacted using the procedure of Example 1 with 4-chloroacetoacetic isopropyl ester. The resultant 4-benzyloxyacetoacetic acid isopropyl ester was subsequently hydrogenolyzed. The 4-hydroxyacetoacetic isopropyl ester thus formed was converted at ambient temperature into tetronic acid by treatment with 18 percent HCl. The total yield, related to the 4-chloroacetoacetic isopropyl ester, was 78 percent. was reacted

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

Procedure: 2-Methyl-1-(2-hydroxyethyl)-imidazo[4,5-c]pyridine (5 g, 28.5 mmole) was added to a suspension of sodium hydride (60% oil dispersion, 2.3 g, 57 mmole) in dry tetrahydrofuran (100 ml) and the mixture was sonicated for 2 hours at room temperature. A solution of isopropyl 4-chloroacetoacetate (5.1 g, 28.5 mmole) in tetrahydrofuran (100 ml) was added dropwise under nitrogen with sonication and the mixture was sonicated for 5 hours at room temperature. 2N Hydrochloric acid (100 ml) was added and the tetrahydrofuran removed under reduced pressure. The aqueous solution was washed with methylene chloride (2×50 ml), neutralised with potassium carbonate and extracted with ethyl acetate (3×25 ml). The combined extracts were washed with water, dried over magnesium sulphate and evaporated. The residue was chromatographed on silica, eluting with ethyl acetate containing 10% isopropyl alcohol to yield isopropyl 4-[2-(2-methyl-1-imidazo[4,5-c]pyridyl)ethoxy]-3-ketobutanoate (5.3 g, 58%). Rf (silica; methanol, ethyl acetate 1:4) 0.13; N.M.R. (CDCl3) δ=1.05 (d, J=6 Hz, 6H); 2.50 (s, 3H); 3.15 (s, 2H); 3.67 (t, J=5.5 Hz, 2H); 3.93 (s, 2H); 4.19 (t, J=5.5 Hz, 2H); 4.8 (m, 1H); 7.11-8.19 (m, 3H). the mixture was sonicated for 2 hours at room temperature the mixture was sonicated for 5 hours at room temperature the tetrahydrofuran removed under reduced pressure The aqueous solution was washed with methylene chloride (2×50 ml) extracted with ethyl acetate (3×25 ml) The combined extracts were washed with water dried over magnesium sulphate evaporated The residue was chromatographed on silica eluting with ethyl acetate containing 10% isopropyl alcohol

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

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

Procedure: The title compound was prepared as described in Example 1 from pyridine and isopropyl 4-chloroacetoacetate in a yield of 71%.

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

Procedure: Sodium benzylate in tetrahydrofuran was reacted using the procedure of Example 1 with 4-chloroacetoacetic isopropyl ester. The resultant 4-benzyloxyacetoacetic acid isopropyl ester was subsequently hydrogenolyzed. The 4-hydroxyacetoacetic isopropyl ester thus formed was converted at ambient temperature into tetronic acid by treatment with 18 percent HCl. The total yield, related to the 4-chloroacetoacetic isopropyl ester, was 78 percent. was reacted

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

Procedure: 2-Methyl-1-(2-hydroxyethyl)-imidazo[4,5-c]pyridine (5 g, 28.5 mmole) was added to a suspension of sodium hydride (60% oil dispersion, 2.3 g, 57 mmole) in dry tetrahydrofuran (100 ml) and the mixture was sonicated for 2 hours at room temperature. A solution of isopropyl 4-chloroacetoacetate (5.1 g, 28.5 mmole) in tetrahydrofuran (100 ml) was added dropwise under nitrogen with sonication and the mixture was sonicated for 5 hours at room temperature. 2N Hydrochloric acid (100 ml) was added and the tetrahydrofuran removed under reduced pressure. The aqueous solution was washed with methylene chloride (2×50 ml), neutralised with potassium carbonate and extracted with ethyl acetate (3×25 ml). The combined extracts were washed with water, dried over magnesium sulphate and evaporated. The residue was chromatographed on silica, eluting with ethyl acetate containing 10% isopropyl alcohol to yield isopropyl 4-[2-(2-methyl-1-imidazo[4,5-c]pyridyl)ethoxy]-3-ketobutanoate (5.3 g, 58%). Rf (silica; methanol, ethyl acetate 1:4) 0.13; N.M.R. (CDCl3) δ=1.05 (d, J=6 Hz, 6H); 2.50 (s, 3H); 3.15 (s, 2H); 3.67 (t, J=5.5 Hz, 2H); 3.93 (s, 2H); 4.19 (t, J=5.5 Hz, 2H); 4.8 (m, 1H); 7.11-8.19 (m, 3H). the mixture was sonicated for 2 hours at room temperature the mixture was sonicated for 5 hours at room temperature the tetrahydrofuran removed under reduced pressure The aqueous solution was washed with methylene chloride (2×50 ml) extracted with ethyl acetate (3×25 ml) The combined extracts were washed with water dried over magnesium sulphate evaporated The residue was chromatographed on silica eluting with ethyl acetate containing 10% isopropyl alcohol