methyl 5-cyanopentanoate

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:; See reaction.notes.procedure_details.

Procedure: Add sodium carbonate (4.5 g, 42 mmol) to a solution of commercially available 5-cyano-pentanoic acid methyl ester (5.0 g, 35 mmol) and hydroxylamine hydrochloride (2.9 g, 42 mmol) in ethanol (100 mL) at room temperature under nitrogen and heat the mixture at reflux for 5.5 h. Filter the mixture through celite and remove the solvent under reduced pressure to provide crude methyl 5-(N-hydroxycarbamimidoyl)pentanoate (5.3 g, 87% yield), which is carried forward without further purification. heat the mixture at reflux for 5.5 h Filter the mixture through celite remove the solvent under reduced pressure

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

Procedure: Add sodium carbonate (4.5 g, 42 mmol) to a solution of commercially available 5-cyano-pentanoic acid methyl ester (5.0 g, 35 mmol) and hydroxylamine hydrochloride (2.9 g, 42 mmol) in ethanol (100 mL) at room temperature under nitrogen and heat the mixture at reflux for 5.5 h. Filter the mixture through celite and remove the solvent under reduced pressure to provide crude methyl 5-(N-hydroxycarbamimidoyl)pentanoate (5.3 g, 87% yield), which is carried forward without further purification. heat the mixture at reflux for 5.5 h Filter the mixture through celite remove the solvent under reduced pressure

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

Procedure: Methyl 5-cyanopentanoate (4.8 g, 34 mmol) is dissolved in toluene, triethylammonium chloride (14 g, 102 mmol) and sodium azide (6.63, 102 mmol) is added. The mixture is heated to reflux for overnight. The reaction mixture is cooled to room temperature, water is added to extract (3×100 mL) methyl 5-tetrazol-5-ylpentanoate from the organic. To the aqueous phase, concentrate HCl is added to adjust pH to 2. The product is extracted from the aqueous solution with EtOAc (3×50 mL). The organic is combined, dried and concentrated to yield 4.25 g (68%) of methyl 5-tetrazol-5-ylpentanoate. The mixture is heated to reflux for overnight to extract (3×100 mL) methyl 5-tetrazol-5-ylpentanoate from the organic To the aqueous phase, concentrate HCl is added The product is extracted from the aqueous solution with EtOAc (3×50 mL) dried concentrated

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

Procedure: Methyl 5-cyanopentanoate (4.8 g, 34 mmol) is dissolved in toluene, triethylammonium chloride (14 g, 102 mmol) and sodium azide (6.63, 102 mmol) is added. The mixture is heated to reflux for overnight. The reaction mixture is cooled to room temperature, water is added to extract (3×100 mL) methyl 5-tetrazol-5-ylpentanoate from the organic. To the aqueous phase, concentrate HCl is added to adjust pH to 2. The product is extracted from the aqueous solution with EtOAc (3×50 mL). The organic is combined, dried and concentrated to yield 4.25 g (68%) of methyl 5-tetrazol-5-ylpentanoate. The mixture is heated to reflux for overnight to extract (3×100 mL) methyl 5-tetrazol-5-ylpentanoate from the organic To the aqueous phase, concentrate HCl is added The product is extracted from the aqueous solution with EtOAc (3×50 mL) dried concentrated

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

Procedure: Potassium Cyanide (4 g, 61.44 mmol) is dissolved in 70 mL water and 200 mL methanol. To the solution 10 g (51.2 mmol) of methyl 5-bromopentanoate is added and the mixture is refluxed overnight. The reaction mixture is concentrated to dryness. To the residue, 100 mL of EtOAc is added to extract the product. The organic is washed with water three times, dried and concentrated to yield 5.37 g (74%) of methyl 5-cyanopentanoate as an oil. the mixture is refluxed overnight The reaction mixture is concentrated to dryness To the residue, 100 mL of EtOAc is added to extract the product The organic is washed with water three times dried concentrated

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

Procedure: Bubble hydrogen chloride (g) through a 0° C. solution of 5-cyano-pentanoic acid methyl ester (3.0 mL; 1.00 equiv; 22.02 mmoles) in methanol (5 mL), and ethyl ether (10 mL) for 1 hour. Allow the solution to warm to room temperature then add 50 mL ethyl ether, stir vigorously for 15 minutes, then filter and collect the resulting precipitate. Wash the solid with ethyl ether to afford methyl 6-imino-6-methoxy-hexanoate (3.82 g; 83%): 1H NMR (DMSO) δ 1.47-1.62 (m, 4H), 2.31 (t, 2H), 2.59 (t, 2H), 3.56 (s, 3H), 4.03 (s, 3H). filter collect the resulting precipitate Wash the solid with ethyl ether

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

Procedure: Bubble hydrogen chloride (g) through a 0° C. solution of 5-cyano-pentanoic acid methyl ester (3.0 mL; 1.00 equiv; 22.02 mmoles) in methanol (5 mL), and ethyl ether (10 mL) for 1 hour. Allow the solution to warm to room temperature then add 50 mL ethyl ether, stir vigorously for 15 minutes, then filter and collect the resulting precipitate. Wash the solid with ethyl ether to afford methyl 6-imino-6-methoxy-hexanoate (3.82 g; 83%): 1H NMR (DMSO) δ 1.47-1.62 (m, 4H), 2.31 (t, 2H), 2.59 (t, 2H), 3.56 (s, 3H), 4.03 (s, 3H). filter collect the resulting precipitate Wash the solid with ethyl ether

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

Procedure: Methyl 5-cyanopentanoate (4.8 g, 34 mmol) is dissolved in toluene, triethylammonium chloride (14 g, 102 mmol) and sodium azide (6.63, 102 mmol) is added. The mixture is heated to reflux for overnight. The reaction mixture is cooled to room temperature, water is added to extract (3×100 mL) methyl 5-tetrazol-5-ylpentanoate from the organic. To the aqueous phase, concentrate HCl is added to adjust pH to 2. The product is extracted from the aqueous solution with EtOAc (3×50 mL). The organic is combined, dried and concentrated to yield 4.25 g (68%) of methyl 5-tetrazol-5-ylpentanoate. The mixture is heated to reflux for overnight to extract (3×100 mL) methyl 5-tetrazol-5-ylpentanoate from the organic To the aqueous phase, concentrate HCl is added The product is extracted from the aqueous solution with EtOAc (3×50 mL) dried concentrated

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

Procedure: Potassium Cyanide (4 g, 61.44 mmol) is dissolved in 70 mL water and 200 mL methanol. To the solution 10 g (51.2 mmol) of methyl 5-bromopentanoate is added and the mixture is refluxed overnight. The reaction mixture is concentrated to dryness. To the residue, 100 mL of EtOAc is added to extract the product. The organic is washed with water three times, dried and concentrated to yield 5.37 g (74%) of methyl 5-cyanopentanoate as an oil. the mixture is refluxed overnight The reaction mixture is concentrated to dryness To the residue, 100 mL of EtOAc is added to extract the product The organic is washed with water three times dried concentrated