4-cyclopropylbutan-1-ol

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

Procedure: To a stirred 0° C. solution of 683 mg (6.0 mmol) of 4-cyclopropylbutanol and 1.25 mL (9.0 mmol) of triethylamine in 10 mL of CH2Cl2 was added 697 μL (9.0 mmol) of methanesulfonyl chloride dropwise under Ar. The cold bath was allowed to expire over a 2 h period at which time the reaction mixture was diluted with CH2Cl2, washed with cold 1M HCl, water, sat. NaHCO3, brine, dried over MgSO4 and the solvents removed to give the title compound as a yellow oil: washed with cold 1M HCl, water, sat. NaHCO3, brine dried over MgSO4 the solvents removed

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

Procedure: The same reaction as in Example 1 (1b) was conducted using N-(4-hydroxybenzoyl)glycine tert-butyl ester (251 mg, 1.00 mmol) prepared in Example 1 (1a) and 4-cyclopropylbutan-1-ol (which is the compound disclosed in J. Med. Chem., (1998), 41, 1112-1123, 137 mg, 1.20 mmol) to give 257 mg of the title compound (white powder, yield: 88%).

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

Procedure: The same reaction as in Example 1 (1b) was conducted using N-(4-hydroxybenzoyl)glycine tert-butyl ester (251 mg, 1.00 mmol) prepared in Example 1 (1a) and 4-cyclopropylbutan-1-ol (which is the compound disclosed in J. Med. Chem., (1998), 41, 1112-1123, 137 mg, 1.20 mmol) to give 257 mg of the title compound (white powder, yield: 88%).

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

Procedure: The same reaction as in Example 1 (1b) was conducted using N-(4-hydroxybenzoyl)glycine tert-butyl ester (251 mg, 1.00 mmol) prepared in Example 1 (1a) and 4-cyclopropylbutan-1-ol (which is the compound disclosed in J. Med. Chem., (1998), 41, 1112-1123, 137 mg, 1.20 mmol) to give 257 mg of the title compound (white powder, yield: 88%).

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

Procedure: To a stirred 0° C. solution of 683 mg (6.0 mmol) of 4-cyclopropylbutanol and 1.25 mL (9.0 mmol) of triethylamine in 10 mL of CH2Cl2 was added 697 μL (9.0 mmol) of methanesulfonyl chloride dropwise under Ar. The cold bath was allowed to expire over a 2 h period at which time the reaction mixture was diluted with CH2Cl2, washed with cold 1M HCl, water, sat. NaHCO3, brine, dried over MgSO4 and the solvents removed to give the title compound as a yellow oil: washed with cold 1M HCl, water, sat. NaHCO3, brine dried over MgSO4 the solvents removed

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

Procedure: To a stirred 0° C. solution of 683 mg (6.0 mmol) of 4-cyclopropylbutanol and 1.25 mL (9.0 mmol) of triethylamine in 10 mL of CH2Cl2 was added 697 μL (9.0 mmol) of methanesulfonyl chloride dropwise under Ar. The cold bath was allowed to expire over a 2 h period at which time the reaction mixture was diluted with CH2Cl2, washed with cold 1M HCl, water, sat. NaHCO3, brine, dried over MgSO4 and the solvents removed to give the title compound as a yellow oil: washed with cold 1M HCl, water, sat. NaHCO3, brine dried over MgSO4 the solvents removed

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Jones reagent is prepared by carefully adding H2SO4 (321 mL) to a cold solution of CrO3 (366 g) in H2O (600 mL) over a period of 0.5 h. In a 5-L 3-neck flask, equipped with mechanical stirrer, internal thermometer, and 1-L addition funnel is placed a solution of 4-cyclopropylbutan-1-ol (127.0 g) in acetone (300 mL). Stirring is commenced, and the solution is cooled below -10° C. with an ice/MeOH bath. The Jones reagent is added at a rate such that the temperature of the reaction mixture never exceeds +10° C. The reaction mixture becomes dark green and heterogenous. 300 mL of Jones reagent is added over 3.5 h and the reaction appears to be complete by TLC (hexane:EtOAc:HOAc, 3:1:0.05). An additional 50 mL Jones reagent is added, and the red color of the reagent persists. The reaction is quenched by the addition of isopropanol (80 mL), and the mixture is allowed to warm to 23° C. A small amount of green precipitate is filtered off, rinsed with acetone (3×200 mL), and discarded. The filtrate is evaporated to a biphasic mixture, poured onto 1.8 kg ice/water, and made alkaline to indicator paper with 50 wt % NaOH (133 g) added in portions. The resulting green solution is filtered to remove a small amount of solids which are discarded. The filtrate is extracted with Et20 (2×40 mL), and the Et20 layers are dried and evaporated to yield 4-cyclopropylbutyl 4-cyclopropylbutanoate. The aqueous layer is cooled in ice while it is acidified with 12N HCl (139 g). The resulting solution is extracted with EtOAc (3×1 L). The aqueous layer is discarded. The organic phases are combined, dried over MgSO4, filtered through paper and evaporated to yield 4-cyclopropylbutanoic acid as a faint green oil. This can be further purified by filtration through Celite and distillation at reduced pressure (0.2-0.4 mbar, 60°-90° C.). In a 5-L 3-neck flask, equipped with mechanical stirrer the solution is cooled below -10° C. with an ice/MeOH bath The reaction is quenched by the addition of isopropanol (80 mL) A small amount of green precipitate is filtered off rinsed with acetone (3×200 mL) The filtrate is evaporated to a biphasic mixture poured onto 1.8 kg ice/water added in portions The resulting green solution is filtered to remove a small amount of solids which The filtrate is extracted with Et20 (2×40 mL) the Et20 layers are dried evaporated

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Jones reagent is prepared by carefully adding H2SO4 (321 mL) to a cold solution of CrO3 (366 g) in H2O (600 mL) over a period of 0.5 h. In a 5-L 3-neck flask, equipped with mechanical stirrer, internal thermometer, and 1-L addition funnel is placed a solution of 4-cyclopropylbutan-1-ol (127.0 g) in acetone (300 mL). Stirring is commenced, and the solution is cooled below -10° C. with an ice/MeOH bath. The Jones reagent is added at a rate such that the temperature of the reaction mixture never exceeds +10° C. The reaction mixture becomes dark green and heterogenous. 300 mL of Jones reagent is added over 3.5 h and the reaction appears to be complete by TLC (hexane:EtOAc:HOAc, 3:1:0.05). An additional 50 mL Jones reagent is added, and the red color of the reagent persists. The reaction is quenched by the addition of isopropanol (80 mL), and the mixture is allowed to warm to 23° C. A small amount of green precipitate is filtered off, rinsed with acetone (3×200 mL), and discarded. The filtrate is evaporated to a biphasic mixture, poured onto 1.8 kg ice/water, and made alkaline to indicator paper with 50 wt % NaOH (133 g) added in portions. The resulting green solution is filtered to remove a small amount of solids which are discarded. The filtrate is extracted with Et20 (2×40 mL), and the Et20 layers are dried and evaporated to yield 4-cyclopropylbutyl 4-cyclopropylbutanoate. The aqueous layer is cooled in ice while it is acidified with 12N HCl (139 g). The resulting solution is extracted with EtOAc (3×1 L). The aqueous layer is discarded. The organic phases are combined, dried over MgSO4, filtered through paper and evaporated to yield 4-cyclopropylbutanoic acid as a faint green oil. This can be further purified by filtration through Celite and distillation at reduced pressure (0.2-0.4 mbar, 60°-90° C.). In a 5-L 3-neck flask, equipped with mechanical stirrer the solution is cooled below -10° C. with an ice/MeOH bath The reaction is quenched by the addition of isopropanol (80 mL) A small amount of green precipitate is filtered off rinsed with acetone (3×200 mL) The filtrate is evaporated to a biphasic mixture poured onto 1.8 kg ice/water added in portions The resulting green solution is filtered to remove a small amount of solids which The filtrate is extracted with Et20 (2×40 mL) the Et20 layers are dried evaporated

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Jones reagent is prepared by carefully adding H2SO4 (321 mL) to a cold solution of CrO3 (366 g) in H2O (600 mL) over a period of 0.5 h. In a 5-L 3-neck flask, equipped with mechanical stirrer, internal thermometer, and 1-L addition funnel is placed a solution of 4-cyclopropylbutan-1-ol (127.0 g) in acetone (300 mL). Stirring is commenced, and the solution is cooled below -10° C. with an ice/MeOH bath. The Jones reagent is added at a rate such that the temperature of the reaction mixture never exceeds +10° C. The reaction mixture becomes dark green and heterogenous. 300 mL of Jones reagent is added over 3.5 h and the reaction appears to be complete by TLC (hexane:EtOAc:HOAc, 3:1:0.05). An additional 50 mL Jones reagent is added, and the red color of the reagent persists. The reaction is quenched by the addition of isopropanol (80 mL), and the mixture is allowed to warm to 23° C. A small amount of green precipitate is filtered off, rinsed with acetone (3×200 mL), and discarded. The filtrate is evaporated to a biphasic mixture, poured onto 1.8 kg ice/water, and made alkaline to indicator paper with 50 wt % NaOH (133 g) added in portions. The resulting green solution is filtered to remove a small amount of solids which are discarded. The filtrate is extracted with Et2O (2×40 mL), and the Et2O layers are dried and evaporated to yield 4-cyclopropylbutyl 4-cyclopropylbutanoate. The aqueous layer is cooled in ice while it is acidified with 12N HCl (139 g). The resulting solution is extracted with EtOAc (3×1 L). The aqueous layer is discarded. The organic phases are combined, dried over MgSO4, filtered through paper and evaporated to yield 4-cyclopropylbutanoic acid as a faint green oil. This can be further purified by filtration through Celite and distillation at reduced pressure (0.2-0.4 mbar, 60°-90° C.). In a 5-L 3-neck flask, equipped with mechanical stirrer the solution is cooled below -10° C. with an ice/MeOH bath The reaction is quenched by the addition of isopropanol (80 mL) A small amount of green precipitate is filtered off rinsed with acetone (3×200 mL) The filtrate is evaporated to a biphasic mixture poured onto 1.8 kg ice/water added in portions The resulting green solution is filtered to remove a small amount of solids which The filtrate is extracted with Et2O (2×40 mL) the Et2O layers are dried evaporated

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

Procedure: The same reaction as in Example 1 (1b) was conducted using N-(4-hydroxybenzoyl)glycine tert-butyl ester (251 mg, 1.00 mmol) prepared in Example 1 (1a) and 4-cyclopropylbutan-1-ol (which is the compound disclosed in J. Med. Chem., (1998), 41, 1112-1123, 137 mg, 1.20 mmol) to give 257 mg of the title compound (white powder, yield: 88%).

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

Procedure: The same reaction as in Example 1 (1b) was conducted using N-(4-hydroxybenzoyl)glycine tert-butyl ester (251 mg, 1.00 mmol) prepared in Example 1 (1a) and 4-cyclopropylbutan-1-ol (which is the compound disclosed in J. Med. Chem., (1998), 41, 1112-1123, 137 mg, 1.20 mmol) to give 257 mg of the title compound (white powder, yield: 88%).

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

Procedure: To a stirred 0° C. solution of 683 mg (6.0 mmol) of 4-cyclopropylbutanol and 1.25 mL (9.0 mmol) of triethylamine in 10 mL of CH2Cl2 was added 697 μL (9.0 mmol) of methanesulfonyl chloride dropwise under Ar. The cold bath was allowed to expire over a 2 h period at which time the reaction mixture was diluted with CH2Cl2, washed with cold 1M HCl, water, sat. NaHCO3, brine, dried over MgSO4 and the solvents removed to give the title compound as a yellow oil: washed with cold 1M HCl, water, sat. NaHCO3, brine dried over MgSO4 the solvents removed