7-bromoheptylbenzene

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

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

Procedure: To a solution of 7-phenyl-1-heptanol (29.1 g, 151.3 mmol) in 800 mL CH2Cl2 at room temperature was added CBr4 (60.2 g, 181.6 mmol) then triphenylphosphine (47.6 g, 181.6 mmol). After 30 s, the reaction had turned a light green color. TLC indicated that the reaction was complete at this point. The solvent was removed in vacuo to give a greenish-white semisolid. To this material was added 10% EtOAc:90% Hexanes and the resulting suspension was filtered through a pad of silica gel washing well with the same solvent system. There yielded 57 g of a colorless oil as the desired bromide and triphenylphosphine oxide. This oil was then flash chromatographed (Hexanes) to yield 38.6 g, 100% of the bromide as a colorless oil. 1H NMR (CDCl3) δ1.30-1.49 (m, 6H); 1.60 (quintet, J=8.18 Hz, 2H); 2.60 (t, J=8.18 Hz, 2H); 3.39 (t, J=8.18 Hz, 2H); 7.13-7.20 (m, 3H); 7.21-7.31 (m, 2H). The solvent was removed in vacuo to give a greenish-white semisolid 90% Hexanes and the resulting suspension was filtered through a pad of silica gel washing well with the same solvent system

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

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

Procedure: To a stirred mixture of 5-hydroxy-6-methoxy-4-methyl-8-nitroquinoline (18 g, 0.077 mol) and 1-bromo-7-phenyl heptane [Example 1a] (15 g, 0.059 mol) in HMPA (45 ml) at 130° C., was added, dropwise, during 1 h, a solution of propylene oxide (18 ml) and Et3N (1 ml). After six more hours, second portions of propylene oxide (4 ml) and Et3N (1 ml) were added and heating was continued for 4 h. The cooled mixture was extracted successively with pet ether, Et2O and Me2CO. The residue returned 2.5 g of starting material (i.e., 5-hydroxy-6-methoxy-4-methyl-8-nitroquinoline). The combined pet ether and Et2O extracts were washed (H2O, dil NaOH, H2O) dried (Na2SO4) and concentrated to a viscous oil. This material was dissolved in CHCl3, placed on a silica gel column (200 g) and eluted with CHCl3. Concentration of the eluates and crystallization of the residue from pet ether (Darco) gave 12 g, (50%) of 6-methoxy-4-methyl-8-nitro-5-(7-phenyl heptoxy) quinoline as yellow crystals, mp 53°-54° C. was added heating was continued for 4 h The cooled mixture was extracted successively with pet ether, Et2O and Me2CO The combined pet ether and Et2O extracts were washed (H2O, dil NaOH, H2O) dried (Na2SO4) concentrated to a viscous oil This material was dissolved in CHCl3 eluted with CHCl3 Concentration of the eluates and crystallization of the residue from pet ether (Darco)

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

Procedure: To a stirred mixture of 5-hydroxy-6-methoxy-4-methyl-8-nitroquinoline (18 g, 0.077 mol) and 1-bromo-7-phenyl heptane [Example 1a] (15 g, 0.059 mol) in HMPA (45 ml) at 130° C., was added, dropwise, during 1 h, a solution of propylene oxide (18 ml) and Et3N (1 ml). After six more hours, second portions of propylene oxide (4 ml) and Et3N (1 ml) were added and heating was continued for 4 h. The cooled mixture was extracted successively with pet ether, Et2O and Me2CO. The residue returned 2.5 g of starting material (i.e., 5-hydroxy-6-methoxy-4-methyl-8-nitroquinoline). The combined pet ether and Et2O extracts were washed (H2O, dil NaOH, H2O) dried (Na2SO4) and concentrated to a viscous oil. This material was dissolved in CHCl3, placed on a silica gel column (200 g) and eluted with CHCl3. Concentration of the eluates and crystallization of the residue from pet ether (Darco) gave 12 g, (50%) of 6-methoxy-4-methyl-8-nitro-5-(7-phenyl heptoxy) quinoline as yellow crystals, mp 53°-54° C. was added heating was continued for 4 h The cooled mixture was extracted successively with pet ether, Et2O and Me2CO The combined pet ether and Et2O extracts were washed (H2O, dil NaOH, H2O) dried (Na2SO4) concentrated to a viscous oil This material was dissolved in CHCl3 eluted with CHCl3 Concentration of the eluates and crystallization of the residue from pet ether (Darco)

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

Procedure: To a stirred solution of 1,7-dibromoheptane (49 g, 0.18 mol) (Aldrich) in THF (300 ml), at -30° C. to -40° C., under N2, was added, dropwise, during 3 h, a solution of phenyllithium (15 g, 0.18 mol) in cyclohexane-ether (2.0M solution, Aldrich). The reaction was allowed to stir at -10° C. to -20° C. for 3 h and at room temperature overnight. After slow, careful dilution with H2O (50 ml), the aqueous layer was extracted with Et2O (2×150 ml). The extracts and the organic layer were combined, dried (Na2SO4) and concentrated to a yellow oil. Distillation through a Vigreaux column provided 22.5 g of 1-bromo-7-phenylheptane, bp 84°-88° C. (0.2 mm), nD24 1.5220. After slow, careful dilution with H2O (50 ml), the aqueous layer was extracted with Et2O (2×150 ml) dried (Na2SO4) concentrated to a yellow oil Distillation through a Vigreaux column

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

Procedure: Starting with methyl 5-(pyridin-2-yl)-[1,3,4]-oxadiazole-2-carboxylate and 7-bromoheptylbenzene, the title compound (25 mg, 41%) was obtained as a white solid, using a procedure similar to Example 1. 1H NMR (400 MHz, CDCl3) 1.38 (m, 6H), 1.63 (quintet, J=7.3 Hz, 2H), 1.80 (quintet, J=7.0 Hz, 2H), 2.61 (dd, J=7.9, 7.6 Hz, 2H), 3.21 (t, J=7.5 Hz, 2H), 7.16-7.19 (m, 3H), 7.26-7.30 (m, 2H), 7.54 (ddd, J=7.6, 4.7, 0.9 Hz, 1H), 7.94 (td, J=7.8,1.8 Hz, 1H), 8.30 (d, J=7.9 Hz, 1H), 8.85 (d, J=4.7 Hz, 1H); 13C NMR (CDCl3, 100 MHz) 23.6, 28.9, 29.0, 29.1, 31.4, 35.7, 35.9, 40.1, 124.0, 125.6, 126.7, 128.2, 128.4, 137.3, 142.6, 142.7, 150.8, 161.2, 165.1, 187.2; MALDI-FTMS m/z 350.1859 (C21H23N3O2+H+ requires 350.1863).

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

Procedure: Starting with methyl 5-(pyridin-2-yl)-[1,3,4]-oxadiazole-2-carboxylate and 7-bromoheptylbenzene, the title compound (25 mg, 41%) was obtained as a white solid, using a procedure similar to Example 1. 1H NMR (400 MHz, CDCl3) 1.38 (m, 6H), 1.63 (quintet, J=7.3 Hz, 2H), 1.80 (quintet, J=7.0 Hz, 2H), 2.61 (dd, J=7.9, 7.6 Hz, 2H), 3.21 (t, J=7.5 Hz, 2H), 7.16-7.19 (m, 3H), 7.26-7.30 (m, 2H), 7.54 (ddd, J=7.6, 4.7, 0.9 Hz, 1H), 7.94 (td, J=7.8,1.8 Hz, 1H), 8.30 (d, J=7.9 Hz, 1H), 8.85 (d, J=4.7 Hz, 1H); 13C NMR (CDCl3, 100 MHz) 23.6, 28.9, 29.0, 29.1, 31.4, 35.7, 35.9, 40.1, 124.0, 125.6, 126.7, 128.2, 128.4, 137.3, 142.6, 142.7, 150.8, 161.2, 165.1, 187.2; MALDI-FTMS m/z 350.1859 (C21H23N3O2+H+ requires 350.1863).

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

Procedure: To a solution of 7-phenyl-1-heptanol (29.1 g, 151.3 mmol) in 800 mL CH2Cl2 at room temperature was added CBr4 (60.2 g, 181.6 mmol) then triphenylphosphine (47.6 g, 181.6 mmol). After 30 s, the reaction had turned a light green color. TLC indicated that the reaction was complete at this point. The solvent was removed in vacuo to give a greenish-white semisolid. To this material was added 10% EtOAc:90% Hexanes and the resulting suspension was filtered through a pad of silica gel washing well with the same solvent system. There yielded 57 g of a colorless oil as the desired bromide and triphenylphosphine oxide. This oil was then flash chromatographed (Hexanes) to yield 38.6 g, 100% of the bromide as a colorless oil. 1H NMR (CDCl3) δ1.30-1.49 (m, 6H); 1.60 (quintet, J=8.18 Hz, 2H); 2.60 (t, J=8.18 Hz, 2H); 3.39 (t, J=8.18 Hz, 2H); 7.13-7.20 (m, 3H); 7.21-7.31 (m, 2H). The solvent was removed in vacuo to give a greenish-white semisolid 90% Hexanes and the resulting suspension was filtered through a pad of silica gel washing well with the same solvent system

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

Procedure: To a solution of 7-phenyl-1-heptanol (29.1 g, 151.3 mmol) in 800 mL CH2Cl2 at room temperature was added CBr4 (60.2 g, 181.6 mmol) then triphenylphosphine (47.6 g, 181.6 mmol). After 30 s, the reaction had turned a light green color. TLC indicated that the reaction was complete at this point. The solvent was removed in vacuo to give a greenish-white semisolid. To this material was added 10% EtOAc:90% Hexanes and the resulting suspension was filtered through a pad of silica gel washing well with the same solvent system. There yielded 57 g of a colorless oil as the desired bromide and triphenylphosphine oxide. This oil was then flash chromatographed (Hexanes) to yield 38.6 g, 100% of the bromide as a colorless oil. 1H NMR (CDCl3) δ1.30-1.49 (m, 6H); 1.60 (quintet, J=8.18 Hz, 2H); 2.60 (t, J=8.18 Hz, 2H); 3.39 (t, J=8.18 Hz, 2H); 7.13-7.20 (m, 3H); 7.21-7.31 (m, 2H). The solvent was removed in vacuo to give a greenish-white semisolid 90% Hexanes and the resulting suspension was filtered through a pad of silica gel washing well with the same solvent system

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

Procedure: ) To a solution of N-[(2-methylphenyl)methylene]-1,1-dimethylethanamine (5.0 g, 0.03 mol) and N,N,N',N'-tetramethylethylene diamine (3.31 g, 0.03 mol) in tetrahydrofuran (40 mL), n-butyl lithium (2.5M, 11.4 mL, 0.03 mol) at 0° C. was slowly added. The solution was stirred for an additional 30 min followed by the quick addition of 1-bromo-7-phenylheptane (7.28 g, 0.03 mol) in tetrahydrofuran (10 mL). The reaction mixture was allowed to warm to room temperature and stirring was continued for 15 h. The reaction mixture was quenched with 10% aqueous hydrochloric acid (50 mL) and stirred for 30 min. The layers were separated, methylene chloride (50 mL) was added to the organic layer and the organics were washed with saturated brine solution (50 mL). The organics were then dried (magnesium sulfate), and concentrated to an oil to yield 2-(8-phenyloctyl)benzaldehyde (3.8 g, 45%): IR (neat film) 2920, 2880, 1695, 1600, 1455 cm-1 ; 1H NMR (CDCl3, 400 MHz) δ 10.25 (s, 1 H), 7.80 (dd, 1 H, J=1.2 and 7.7 Hz), 7.45 (m, 1 H), 7.33-7.13 (m, 7 H), 2.98 (t, 2 H, J=7.7 Hz), 2.58 (t, 2 H, J=7.7 Hz), 1.58 (m, 4 H), 1.30 (m, 8 H). stirring was continued for 15 h The reaction mixture was quenched with 10% aqueous hydrochloric acid (50 mL) stirred for 30 min The layers were separated methylene chloride (50 mL) was added to the organic layer the organics were washed with saturated brine solution (50 mL) The organics were then dried (magnesium sulfate) concentrated to an oil

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

Procedure: ) To a solution of N-[(2-methylphenyl)methylene]-1,1-dimethylethanamine (5.0 g, 0.03 mol) and N,N,N',N'-tetramethylethylene diamine (3.31 g, 0.03 mol) in tetrahydrofuran (40 mL), n-butyl lithium (2.5M, 11.4 mL, 0.03 mol) at 0° C. was slowly added. The solution was stirred for an additional 30 min followed by the quick addition of 1-bromo-7-phenylheptane (7.28 g, 0.03 mol) in tetrahydrofuran (10 mL). The reaction mixture was allowed to warm to room temperature and stirring was continued for 15 h. The reaction mixture was quenched with 10% aqueous hydrochloric acid (50 mL) and stirred for 30 min. The layers were separated, methylene chloride (50 mL) was added to the organic layer and the organics were washed with saturated brine solution (50 mL). The organics were then dried (magnesium sulfate), and concentrated to an oil to yield 2-(8-phenyloctyl)benzaldehyde (3.8 g, 45%): IR (neat film) 2920, 2880, 1695, 1600, 1455 cm-1 ; 1H NMR (CDCl3, 400 MHz) δ 10.25 (s, 1 H), 7.80 (dd, 1 H, J=1.2 and 7.7 Hz), 7.45 (m, 1 H), 7.33-7.13 (m, 7 H), 2.98 (t, 2 H, J=7.7 Hz), 2.58 (t, 2 H, J=7.7 Hz), 1.58 (m, 4 H), 1.30 (m, 8 H). stirring was continued for 15 h The reaction mixture was quenched with 10% aqueous hydrochloric acid (50 mL) stirred for 30 min The layers were separated methylene chloride (50 mL) was added to the organic layer the organics were washed with saturated brine solution (50 mL) The organics were then dried (magnesium sulfate) concentrated to an oil