2-Bromobutyryl chloride

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

Procedure: 30 g (0.092 mole) of diethyl N-(2,4-dimethoxybenzyl)-amino-malonate prepared according to paragraph (b) of Example 1 are dissolved in a mixture of 90 ml of benzene and 15.6 ml (11.2 g, 0.111 mole) of triethyl amine and thereafter 20.5 g (0.111 mole) of 2-bromo butyric acid chloride are added dropwise under external ice-cooling. The reaction mixture is stirred under cooling for half an hour and thereafter at room temperature for half an hour. The precipitated crystalline substance is filtered off and washed twice with 20 ml of benzene. To the combined benzene mother liquor 31.2 g (22.4 g, 0.222 mole) of triethyl amine are added and the mixture is boiled for 6 hours. The precipitated crystalline substance is cooled and filtered. The mother liquor is extracted successively with 100 ml of water, twice with 100 ml of diluted hydrochloric acid each (a mixture of 90 ml of water and 10 ml of hydrochloric acid) and twice with 100 ml of water each. The organic layer is dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated. The residual oil is made crystalline by rubbing with petrolether. Thus 31.5 g of diethyl 1-(2,4-dimethoxy-benzyl)-3-ethyl-4-oxo-2,2-azetidinedicarboxylate are obtained. M.p.: 69° C. (from a mixture of benzene and petrolether). cooling under cooling for half an hour at room temperature for half an hour The precipitated crystalline substance is filtered off washed twice with 20 ml of benzene The precipitated crystalline substance is cooled filtered The mother liquor is extracted successively with 100 ml of water, twice with 100 ml of diluted hydrochloric acid each ( a mixture of 90 ml of water and 10 ml of hydrochloric acid) and twice with 100 ml of water each The organic layer is dried over anhydrous magnesium sulfate filtered the filtrate is evaporated

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

Procedure: 30 g (0.092 mole) of diethyl N-(2,4-dimethoxybenzyl)-amino-malonate prepared according to paragraph (b) of Example 1 are dissolved in a mixture of 90 ml of benzene and 15.6 ml (11.2 g, 0.111 mole) of triethyl amine and thereafter 20.5 g (0.111 mole) of 2-bromo butyric acid chloride are added dropwise under external ice-cooling. The reaction mixture is stirred under cooling for half an hour and thereafter at room temperature for half an hour. The precipitated crystalline substance is filtered off and washed twice with 20 ml of benzene. To the combined benzene mother liquor 31.2 g (22.4 g, 0.222 mole) of triethyl amine are added and the mixture is boiled for 6 hours. The precipitated crystalline substance is cooled and filtered. The mother liquor is extracted successively with 100 ml of water, twice with 100 ml of diluted hydrochloric acid each (a mixture of 90 ml of water and 10 ml of hydrochloric acid) and twice with 100 ml of water each. The organic layer is dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated. The residual oil is made crystalline by rubbing with petrolether. Thus 31.5 g of diethyl 1-(2,4-dimethoxy-benzyl)-3-ethyl-4-oxo-2,2-azetidinedicarboxylate are obtained. M.p.: 69° C. (from a mixture of benzene and petrolether). cooling under cooling for half an hour at room temperature for half an hour The precipitated crystalline substance is filtered off washed twice with 20 ml of benzene The precipitated crystalline substance is cooled filtered The mother liquor is extracted successively with 100 ml of water, twice with 100 ml of diluted hydrochloric acid each ( a mixture of 90 ml of water and 10 ml of hydrochloric acid) and twice with 100 ml of water each The organic layer is dried over anhydrous magnesium sulfate filtered the filtrate is evaporated

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

Procedure: 65.96 g (355.7 mmol) of α-bromobutyric acid chloride is added in drops at 0° C. to 100 g (296.4 mmol) of glycine benzyl ester p-toluenesulfonic acid salt and 89.98 g (889.2 mmol) of triethylamine in 500 ml of methylene chloride. In this case, the temperature remains between 0° C.-5° C. 1000 ml of 5% aqueous hydrochloric acid is added, and the organic phase is separated. remains between 0° C.-5° C the organic phase is separated

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

Procedure: 65.96 g (355.7 mmol) of α-bromobutyric acid chloride is added in drops at 0° C. to 100 g (296.4 mmol) of glycine benzyl ester p-toluenesulfonic acid salt and 89.98 g (889.2 mmol) of triethylamine in 500 ml of methylene chloride. In this case, the temperature remains between 0° C.-5° C. 1000 ml of 5% aqueous hydrochloric acid is added, and the organic phase is separated. The organic phase is extracted once more with 500 ml of 5% aqueous hydrochloric acid, dried on magnesium sulfate and evaporated to dryness in a vacuum. The residue is recrystallized from diisopropyl ether. remains between 0° C.-5° C the organic phase is separated The organic phase is extracted once more with 500 ml of 5% aqueous hydrochloric acid dried on magnesium sulfate evaporated to dryness in a vacuum The residue is recrystallized from diisopropyl ether

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

Procedure: 65.96 g (355.7 mmol) of α-bromobutyric acid chloride is added in drops at 0° C. to 100 g (296.4 mmol) of glycine benzyl ester p-toluenesulfonic acid salt and 89.98 g (889.2 mmol) of triethylamine in 500 ml of methylene chloride. In this case, the temperature remains between 0° C.-5° C. 1000 ml of 5% aqueous hydrochloric acid is added, and the organic phase is separated. The organic phase is extracted once more with 500 ml of 5% aqueous hydrochloric acid, dried on magnesium sulfate and evaporated to dryness in a vacuum. The residue is recrystallized from diisopropyl ether. remains between 0° C.-5° C the organic phase is separated The organic phase is extracted once more with 500 ml of 5% aqueous hydrochloric acid dried on magnesium sulfate evaporated to dryness in a vacuum The residue is recrystallized from diisopropyl ether

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

Procedure: The title compound was prepared in analogy to Example 40-2 in Scheme 18 by using 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine, 2-bromobutyryl chloride and sodium azide. MS obsd. (ESI+) [(M+H)+] 439, 1H NMR (400 MHz, CD3OD) δ ppm 8.07 (m, 3 H), 7.53 (m, 2 H), 7.45 (m, 2 H), 5.33 (m, 2 H), 4.32 (m, 1 H), 3.59 (m, 2 H), 3.37 (s, 3 H), 2.44 (m, 2 H), 1.70 (d, J=8.02 Hz, 1 H), 1.38 (d, J=2.56 Hz, 2 H), 1.22 (m, 3 H).

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

Procedure: 30 g (0.092 mole) of diethyl N-(2,4-dimethoxybenzyl)-amino-malonate prepared according to paragraph (b) of Example 1 are dissolved in a mixture of 90 ml of benzene and 15.6 ml (11.2 g, 0.111 mole) of triethyl amine and thereafter 20.5 g (0.111 mole) of 2-bromo butyric acid chloride are added dropwise under external ice-cooling. The reaction mixture is stirred under cooling for half an hour and thereafter at room temperature for half an hour. The precipitated crystalline substance is filtered off and washed twice with 20 ml of benzene. To the combined benzene mother liquor 31.2 g (22.4 g, 0.222 mole) of triethyl amine are added and the mixture is boiled for 6 hours. The precipitated crystalline substance is cooled and filtered. The mother liquor is extracted successively with 100 ml of water, twice with 100 ml of diluted hydrochloric acid each (a mixture of 90 ml of water and 10 ml of hydrochloric acid) and twice with 100 ml of water each. The organic layer is dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated. The residual oil is made crystalline by rubbing with petrolether. Thus 31.5 g of diethyl 1-(2,4-dimethoxy-benzyl)-3-ethyl-4-oxo-2,2-azetidinedicarboxylate are obtained. M.p.: 69° C. (from a mixture of benzene and petrolether). cooling under cooling for half an hour at room temperature for half an hour The precipitated crystalline substance is filtered off washed twice with 20 ml of benzene The precipitated crystalline substance is cooled filtered The mother liquor is extracted successively with 100 ml of water, twice with 100 ml of diluted hydrochloric acid each ( a mixture of 90 ml of water and 10 ml of hydrochloric acid) and twice with 100 ml of water each The organic layer is dried over anhydrous magnesium sulfate filtered the filtrate is evaporated

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

Procedure: 65.96 g (355.7 mmol) of α-bromobutyric acid chloride is added in drops at 0° C. to 100 g (296.4 mmol) of glycine benzyl ester p-toluenesulfonic acid salt and 89.98 g (889.2 mmol) of triethylamine in 500 ml of methylene chloride. In this case, the temperature remains between 0° C.-5° C. 1000 ml of 5% aqueous hydrochloric acid is added, and the organic phase is separated. remains between 0° C.-5° C the organic phase is separated