oct-7-enoic acid

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

Procedure: Following the aforementioned procedure, diene was prepared from oct-7-enoic acid and dec-9-en-1-ol. The resulting yellow oil was purified by silica gel chromatography (50:1 hexanes: diethyl ether) to afford the desired product as a colorless oil. IR (neat): 3077 (m), 2926 (s), 2855 (s), 1736 (s), 1641 (m), 1462 (m), 1417 (m), 1351 (m), 1255 (s), 1168 (s), 1113 (m), 1076 (m), 993 (s), 909 (s), 734 (m), 632 (m); 1H NMR (400 MHz, CDCl3): δ 5.86-5.75 (2H, m), 5.02-4.91 (4H, m), 4.05 (2H, t, J=6.8 Hz), 2.29 (2H, t, J=7.6 Hz), 2.08-2.01 (4H, m), 1.67-1.59 (4H, m), 1.42-1.27 (14H, m); 13C NMR (100 MHz, CDCl3): δ 174.0, 139.2, 138.9, 114.5, 114.3, 64.5, 34.4, 33.9, 33.7, 29.5, 29.3, 29.1, 29.0, 28.8, 28.7, 28.6, 26.0, 25.0; HRMS (ESI+) [M+H]+ calcd for C18H33O2: 281.2481. found: 281.2475. The resulting yellow oil was purified by silica gel chromatography (50:1 hexanes: diethyl ether)

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

Procedure: 2-heptenoic acid; 3-heptenoic acid; 4-heptenoic acid; 5-hetpenoic acid; 6-heptenoic acid; 2-hexenoic acid;

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of 11.0 g lithium hydride in 800 ml of anhydrous ether, there was added dropwise 164 g of oct-7-enoic acid (prepared in Example 22 B-2) in 800 ml of anhydrous ether and the mixture was cooled to 0° C. and 650 ml of 2 M methyllithium in ether was added dropwise and then allowed to warm to room temperature and stir for 4.5 hr. This mixture was quenched by pouring the slurry into rapidly stirred 10% aqueous hydrochloric acid (1.2 liter) and wet ice. The resulting mixture was extracted with ether (3×700 ml). The continued ether extracts were washed with 10% aqueous sodium hydroxide and then with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to yield 118.9 g of the title compound having the following physical characteristics: to warm to room temperature This mixture was quenched by pouring the slurry into rapidly stirred 10% aqueous hydrochloric acid (1.2 liter) and wet ice The resulting mixture was extracted with ether (3×700 ml) The continued ether extracts were washed with 10% aqueous sodium hydroxide with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate The solvent was removed in vacuo

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

Procedure: To a stirred solution of 152 g of oct-7-en-1-ol (prepared in Example 22 B-1) in 3.4 liters of acetone there was added 1.4 M of Jones Reagent (986 ml) while the mixture was maintained at less than 10° C. The mixture was stirred for 10 min and was quenched with 100 ml of isopropanol. The acetone volume was reduced in vacuo and the residue was diluted with water and extracted three times with equal volumes of ethyl acetate. The combined ethyl acetate extracts were washed two times with water, then with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated in vacuo to yield 164 g of the title compound having the following physical characteristics: was maintained at less than 10° C was quenched with 100 ml of isopropanol the residue was diluted with water extracted three times with equal volumes of ethyl acetate The combined ethyl acetate extracts were washed two times with water with saturated aqueous sodium chloride, dried over magnesium sulfate evaporated in vacuo

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

Procedure: Following the aforementioned procedure, diene was prepared from oct-7-enoic acid and dec-9-en-1-ol. The resulting yellow oil was purified by silica gel chromatography (50:1 hexanes: diethyl ether) to afford the desired product as a colorless oil. IR (neat): 3077 (m), 2926 (s), 2855 (s), 1736 (s), 1641 (m), 1462 (m), 1417 (m), 1351 (m), 1255 (s), 1168 (s), 1113 (m), 1076 (m), 993 (s), 909 (s), 734 (m), 632 (m); 1H NMR (400 MHz, CDCl3): δ 5.86-5.75 (2H, m), 5.02-4.91 (4H, m), 4.05 (2H, t, J=6.8 Hz), 2.29 (2H, t, J=7.6 Hz), 2.08-2.01 (4H, m), 1.67-1.59 (4H, m), 1.42-1.27 (14H, m); 13C NMR (100 MHz, CDCl3): δ 174.0, 139.2, 138.9, 114.5, 114.3, 64.5, 34.4, 33.9, 33.7, 29.5, 29.3, 29.1, 29.0, 28.8, 28.7, 28.6, 26.0, 25.0; HRMS (ESI+) [M+H]+ calcd for C18H33O2: 281.2481. found: 281.2475. The resulting yellow oil was purified by silica gel chromatography (50:1 hexanes: diethyl ether)

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

Procedure: 2-heptenoic acid; 3-heptenoic acid; 4-heptenoic acid; 5-hetpenoic acid; 6-heptenoic acid; 2-hexenoic acid;

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of 11.0 g lithium hydride in 800 ml of anhydrous ether, there was added dropwise 164 g of oct-7-enoic acid (prepared in Example 22 B-2) in 800 ml of anhydrous ether and the mixture was cooled to 0° C. and 650 ml of 2 M methyllithium in ether was added dropwise and then allowed to warm to room temperature and stir for 4.5 hr. This mixture was quenched by pouring the slurry into rapidly stirred 10% aqueous hydrochloric acid (1.2 liter) and wet ice. The resulting mixture was extracted with ether (3×700 ml). The continued ether extracts were washed with 10% aqueous sodium hydroxide and then with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to yield 118.9 g of the title compound having the following physical characteristics: to warm to room temperature This mixture was quenched by pouring the slurry into rapidly stirred 10% aqueous hydrochloric acid (1.2 liter) and wet ice The resulting mixture was extracted with ether (3×700 ml) The continued ether extracts were washed with 10% aqueous sodium hydroxide with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate The solvent was removed in vacuo

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

Procedure: To a stirred solution of 152 g of oct-7-en-1-ol (prepared in Example 22 B-1) in 3.4 liters of acetone there was added 1.4 M of Jones Reagent (986 ml) while the mixture was maintained at less than 10° C. The mixture was stirred for 10 min and was quenched with 100 ml of isopropanol. The acetone volume was reduced in vacuo and the residue was diluted with water and extracted three times with equal volumes of ethyl acetate. The combined ethyl acetate extracts were washed two times with water, then with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated in vacuo to yield 164 g of the title compound having the following physical characteristics: was maintained at less than 10° C was quenched with 100 ml of isopropanol the residue was diluted with water extracted three times with equal volumes of ethyl acetate The combined ethyl acetate extracts were washed two times with water with saturated aqueous sodium chloride, dried over magnesium sulfate evaporated in vacuo

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

Procedure: The title compound was prepared from 8-chloro-4-hydroxy-2-(4-isopropylthiazole-2-yl)-7-methoxyquinoline (46), oct-7-enoic acid and intermediate 5 following the procedure (Step D-H) reported for 18-[2-[4-(isopropyl)thiazol-2-yl]-7-methoxyquinolin-4-yloxy]-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid 10: m/z=653 (M+H)+.

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

Procedure: A 500-ml four-necked flask equipped with hydrogen bromide inlet, thermometer, 7-octenoic acid inlet and oxygen inlet was charged with 10 g of 7-octenoic acid and 50 ml of toluene. After passing air at 20° C. with stirring at a rate of 10 liters per hour for 30 minutes, hydrogen bromide and a solution of 90 g of 7-octenoic acid in 250 ml of toluene were continuously fed with stirring at the rates of 120 ml/hr and 9 l/hr, respectively. After 3 hours of reaction, the reaction mixture was treated in the same manner as described above under (3) (i) to give 139 g (89% yield) of 8-bromocaprylic acid. A 500-ml four-necked flask equipped with hydrogen bromide inlet at 20° C. with stirring at the rates of 120 ml/hr and 9 l/hr After 3 hours of reaction the reaction mixture was treated in the same manner

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

Procedure: The title compound was prepared from 4-hydroxy-2-(4-isopropylthiazol-2-yl)-7-methoxyquinoline, oct-7-enoic acid and intermediate 5 following the procedure (Step D-H) reported for 18-[2-[4-(isopropyl)thiazol-2-yl]-7-methoxyquinolin-4-yloxy]-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid 10: m/z=619 (M+H)+.

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

Procedure: The title compound was prepared from 4-hydroxy-2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinoline (28), oct-7-enoic acid and intermediate 5 following the procedure (Step D-H) reported for 18-[2-[4-(isopropyl)thiazol-2-yl]-7-methoxyquinolin-4-yloxy]-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid 10: m/z=633 (M+H)+.