1,6-diiodohexane

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

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

Procedure: A mixture of 1,6-diiodohexane (10.14 g, 30 mmol) and the silver salt of 2-hydroxy-1,4-naphthoquinone (2.81 g, 10 mmol) in benzene (60 mL) was stirred for 12 h at room temperature. The reacton mixture was filtered through Celite, concentrated in vacuo, and purified by flash chromatography (hexane/ EtOAc 4:1) to give a yellow solid (2,19 g, 57%); mp 85-87° C.; 1H NMR (CDCl3) 8.12 (dd, J=6.5, 1.0 Hz, 1H), 7.86 (dd, J=6.9, 0.9 Hz, 1H), 7.70 (dt, J=7.6, 1.5 Hz, 1H), 7.58 (dt, J=7.5, 1.3 Hz, 1H), 5.95 (s, 1H), 4.15 (t, J=6.3, 2H), 3.22 (t, J=6.9 Hz, 2H), 1.80-2.05 (m, 4H), 1.45-2.10 (m, 4H). The reacton mixture was filtered through Celite concentrated in vacuo purified by flash chromatography (hexane/ EtOAc 4:1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,6-Diiodohexane (mmol) was added to a solution (30 mL) of dry quinoline, and the solution heated for 24 hours at 65° C. The resulting precipitate was filtered, and the product washed five times with dry diethyl ether. The resulting yellow solid was isolated. 1H NMR (300 MHz, DMSO-D6) δ 9.53 (1H, d, C2-H), 9.29 (1H, d, C3-H), 8.61 (1H, d, C8-H), 8.50 (1H, d, C4-H), 8.29 (1H, t, C7-H), 8.18 (1H, t, C5-H), 8.07 (1H, d, C6-H), 5.09 (2H, t, C′1-CH2), 1.96 (2H, m, C′2-CH2), 1.25 (2H, m, C′3-CH2). The resulting precipitate was filtered the product washed five times with dry diethyl ether The resulting yellow solid was isolated

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,6-Diiodohexane (mmol) was added to a solution (30 mL) of dry pyridine, and the solution heated for 24 hours at 65° C. The resulting precipitate was filtered, and the product washed five times with dry diethyl ether. The resulting yellow solid was isolated. 1H NMR (300 MHz, DMSO-D6) δ 9.11 (2H, d, C2&C6-H), 8.63 (1H, t, C4-H), 8.18 (2H, t, C3&C5-H), 4.59 (2H, t, C′1-CH2), 1.89 (2H, m, C′2-CH2), 1.28 (2H, m, C′3-CH2). The resulting precipitate was filtered the product washed five times with dry diethyl ether The resulting yellow solid was isolated

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,6-Diiodohexane (mmol) was added to a solution (30 mL) of dry pyridine, and the solution heated for 24 hours at 65° C. The resulting precipitate was filtered, and the product washed five times with dry diethyl ether. The resulting yellow solid was isolated. 1H NMR (300 MHz, DMSO-D6) δ 9.11 (2H, d, C2&C6-H), 8.63 (1H, t, C4-H), 8.18 (2H, t, C3&C5-H), 4.59 (2H, t, C′1-CH2), 1.89 (2H, m, C′2-CH2), 1.28 (2H, m, C′3-CH2). The resulting precipitate was filtered the product washed five times with dry diethyl ether The resulting yellow solid was isolated

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

Procedure: A mixture of 1,6-diiodohexane (10.14 g, 30 mmol) and the silver salt of 2-hydroxy-1,4-naphthoquinone (2.81 g, 10 mmol) in benzene (60 mL) was stirred for 12 h at room temperature. The reacton mixture was filtered through Celite, concentrated in vacuo, and purified by flash chromatography (hexane/EtOAc 4:1) to give a yellow solid (2,19 g, 57%); mp 85-87° C.; 1H NMR (CDCl3) 8.12 (dd, J=6.5, 1.0 Hz, 1H), 7.86 (dd, J=6.9, 0.9 Hz, 1H), 7.70 (dt, J=7.6, 1.5 Hz, 1H), 7.58 (dt, J=7.5, 1.3 Hz, 1H), 5.95 (s, 1H), 4.15 (t, J=6.3, 2H), 3.22 (t, J=6.9 Hz, 2H), 1.80-2.05 (m, 4H), 1.45-2.10 (m, 4H). The reacton mixture was filtered through Celite concentrated in vacuo purified by flash chromatography (hexane/EtOAc 4:1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(4-hydroxyphenyl)-1-propanol 35 (3.3 g, 21.7 mmole) and 1,6-di-iodohexane (3.5 g, 8.88 mmole) in dimethylsulfoxide (40 mL) was degassed and saturated with N2 gas and potassium carbonate (4.5 g, 32.56 mmole) was added. The reaction mixture was stirred at 80° C. for 18 h under nitrogen atmosphere and then quenched with brine (150 mL). The product was extracted with EtOAc (200 mL) and the organic extracts were washed with 0.1 M NaOH and brine, and dried with MgSO4. The organics were removed in vacuo to give a pale brown solid. The solid was purified by flash silica column chromatography: 4/1 hexane/EtOAc to 5% MeOH in 1/1 hexane/EtOAc to give 1,6-bis[4-(3-hydroxypropyl)phenoxy]hexane 36 (Rf=0.17 in 1/1 hexane/EtOAc) in 65% yield (2.23 g). 1H-NMR (CD3OD, 299.96 MHz): δ (ppm) 7.08-7.05 (d, 4H), 6.80-6.77 (d, 4H), 3.93-3.89 (t, 4H), 3.56-3.52 (t, 4H), 2.64-2.56 (t, 4H), 1.81-1.69 (m, 8H), 1.44-1.21 (m, 4H). was added quenched with brine (150 mL) The product was extracted with EtOAc (200 mL) the organic extracts were washed with 0.1 M NaOH and brine dried with MgSO4 The organics were removed in vacuo to give a pale brown solid The solid was purified by flash silica column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(4-hydroxyphenyl)-1-propanol 35 (3.3 g, 21.7 mmole) and 1,6-di-iodohexane (3.5 g, 8.88 mmole) in dimethylsulfoxide (40 mL) was degassed and saturated with N2 gas and potassium carbonate (4.5 g, 32.56 mmole) was added. The reaction mixture was stirred at 80° C. for 18 h under nitrogen atmosphere and then quenched with brine (150 mL). The product was extracted with EtOAc (200 mL) and the organic extracts were washed with 0.1 M NaOH and brine, and dried with MgSO4. The organics were removed in vacuo to give a pale brown solid. The solid was purified by flash silica column chromatography: 4/1 hexane/EtOAc to 5% MeOH in 1/1 hexane/EtOAc to give 1,6-bis[4-(3-hydroxypropyl)phenoxy]hexane 36 (Rf=0.17 in 1/1 hexane/EtOAc) in 65% yield (2.23 g). 1H-NMR (CD3OD, 299.96 MHz): δ (ppm) 7.08-7.05 (d, 4H), 6.80-6.77 (d, 4H), 3.93-3.89 (t, 4H), 3.56-3.52 (t, 4H), 2.64-2.56 (t, 4H), 1.81-1.69 (m, 8H), 1.44-1.21 (m, 4H). was added quenched with brine (150 mL) The product was extracted with EtOAc (200 mL) the organic extracts were washed with 0.1 M NaOH and brine dried with MgSO4 The organics were removed in vacuo to give a pale brown solid The solid was purified by flash silica column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(4-hydroxyphenyl)-1-propanol 35 (3.3 g, 21.7 mmole) and 1,6-di-iodohexane (3.5 g, 8.88 mmole) in dimethylsulfoxide (40 mL) was degassed and saturated with N2 gas and potassium carbonate (4.5 g, 32.56 mmole) was added. The reaction mixture was stirred at 80° C. for 18 h under nitrogen atmosphere and then quenched with brine (150 mL). The product was extracted with EtOAc (200 mL) and the organic extracts were washed with 0.1 M NaOH and brine, and dried with MgSO4. The organics were removed in vacuo to give a pale brown solid. The solid was purified by flash silica column chromatography: 4/1 hexane/EtOAc to 5% MeOH in 1/1 hexane/EtOAc to give 1,6-bis[4-(3-hydroxypropyl)phenoxy]hexane 36 (Rf=0.17 in 1/1 hexane/EtOAc) in 65% yield (2.23 g). 1H-NMR (CD3OD, 299.96 MHz): δ (ppm) 7.08-7.05 (d, 4H), 6.80-6.77 (d, 4H), 3.93-3.89 (t, 4H), 3.56-3.52 (t, 4H), 2.64-2.56 (t, 4H), 1.81-1.69 (m, 8H), 1.44-1.21 (m, 4H). was added quenched with brine (150 mL) The product was extracted with EtOAc (200 mL) the organic extracts were washed with 0.1 M NaOH and brine dried with MgSO4 The organics were removed in vacuo to give a pale brown solid The solid was purified by flash silica column chromatography

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

Procedure: A mixture of 1,6-diiodohexane (10.14 g, 30 mmol) and the silver salt of 2-hydroxy-1,4-naphthoquinone (2.81 g, 10 mmol) in benzene (60 mL) was stirred for 12 h at room temperature. The reaction mixture was filtered through Celite, concentrated in vacuo, and purified by flash chromatography (hexane/EtOAc 4:1) to give a yellow solid (2,19 g, 57%); mp 85-87° C.; 1H NMR (CDCl3) 8.12 (dd, J=6.5, 1.0 Hz, 1H), 7.86 (dd, J=6.9, 0.9 Hz, 1H), 7.70 (dt, J=7.6, 1.5 Hz, 1H), 7.58 (dt, J=7.5, 1.3 Hz, 1H), 5.95 (s, 1H), 4.15 (t, J=6.3, 2H), 3.22 (t, J=6.9 Hz, 2H), 1.80-2.05 (m, 4H), 1.45-2.10 (m, 4H). The reaction mixture was filtered through Celite concentrated in vacuo purified by flash chromatography (hexane/EtOAc 4:1)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: At −78° C., butyl lithium (a 1.57M hexane solution; 0.62 ml, 0.966 mmol) was added dropwise to a dimethoxyethane (5 ml) solution of the 2-chloro-3-(4-chlorophenylsulfonylmethyl)pyridine (146 mg, 0.483 mmol) obtained in Example 98. At −78° C., the resulting mixture was stirred for 20 minutes, followed by the addition of 1,6-diiodohexane (0.095 ml, 0.580 mmol). The temperature of the reaction mixture was gradually raised to room temperature, at which stirring was performed for 4 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to flash chromatography on a silica gel column, and the fraction obtained from the 15% ethyl acetate/hexane eluate was concentrated under reduced pressure. The residue thus obtained was purified by high performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to yield the title compound (60 mg, 32%) as a white solid. The resulting solid was washed with hexane-ether and then collected by filtration, whereby the title compound was obtained as a white powder. At −78° C. The temperature of the reaction mixture was gradually raised to room temperature, at which stirring was performed for 4 hours followed by extraction with ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate After filtration the filtrate was concentrated under reduced pressure the fraction obtained from the 15% ethyl acetate/hexane eluate was concentrated under reduced pressure The residue thus obtained was purified by high performance liquid chromatography (

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

Procedure: A mixture of 1,6-diiodohexane (10. 14 g, 30 mmol) and the silver salt of 2-hydroxy-1,4-naphthoquinone (2.81 g, 10 mmol) in benzene (60 mL) was stirred for 12 h at room temperature. The reacton mixture was filtered through Celite, concentrated in vacuo, and purified by flash chromatography (hexane/EtOAc 4:1) to give a yellow solid (2,19 g, 57%); mp 85-87° C.; 1H NMR (CDCl3) 8.12 (dd, J=6.5, 1.0 Hz, 1H), 7.86 (dd, J=6.9, 0.9 Hz, 1H), 7.70 (dt, J=7.6, 1.5 Hz, 1H), 7.58 (dt, J=7.5, 1.3 Hz, 1H), 5.95 (s, 1H), 4.15 (t, J=6.3, 2H), 3.22 (t, J=6.9 Hz, 2H), 1.80-2.05 (m, 4H), 1.45-2.10 (m, 4H). The reacton mixture was filtered through Celite concentrated in vacuo purified by flash chromatography (hexane/EtOAc 4:1)