1-(4-fluorophenyl)propan-1-ol

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 2.26 g (14.65 mmol) of 3-(4-fluorophenyl propanol and 3.6 mL (44 mmol) of pyridine in 40 mL of CH2Cl2 at 0° C. was added 5.1 g (29.3 mmol) of methanesulfonic anhydride and the reaction mixture was sitirred for 4 h at rt. The reaction mixture was partitioned between 100 mL of CH2Cl2 and 20 of sat'd NaHCO3 solution. The organic fraction was washed 3 times with sat'd NaHCO3 solution and sat'd NaCl solution, dried over MgSO4 and the filtrate was concentrated several times from heptane to remove pyridine. To the residue in 50 mL of acetone was added 6 g (44 mmol) of LiI and the reaction mixture was Stirred for 20 hr. The reaction mixture was poured into 200 mL of H2O and extracted with ether. The combined organic fractions were washed with sat'd NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated. The residue was purified by chromatography (silica, hexanes: ethyl acetate, 9:1) to give 3.25 g of the title compound. The reaction mixture was partitioned between 100 mL of CH2Cl2 and 20 of sat'd NaHCO3 solution The organic fraction was washed 3 times with sat'd NaHCO3 solution dried over MgSO4 the filtrate was concentrated several times from heptane to remove pyridine extracted with ether The combined organic fractions were washed with sat'd NaCl solution dried over MgSO4 filtered the filtrate was concentrated The residue was purified by chromatography (silica, hexanes: ethyl acetate, 9:1)

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

Procedure: The obtained 4-fluorophenylpropan-1-ol (4.83 g, 31.3 mmol) was dissolved in dichloromethane (50 ml), and triethylamine (6.55 ml, 47.0 mmol) and methanesulfonyl chloride (2.91 ml, 37.6 mmol) were added thereto in the ice bath followed by stirring under a nitrogen atmosphere for 30 minutes. The reaction mixture was diluted with dichloromethane (50 ml), and washed with 10% hydrochloric acid and subsequently with a saturated aqueous sodium chloride solution, and then dried over magnesium sulfate. The solvent was evaporated in vacuo, and the residue was dissolved in acetone (100 ml), and then sodium iodide (9.39 g, 62.6 mmol) was added thereto followed by stirring under a nitrogen atmosphere for 2 hours at 50° C. The reaction mixture was diluted with ethyl acetate (250 ml), and washed with 10% aqueous sodium thiosulfate solution and subsequently with a saturated aqueous sodium chloride solution, and then dried over magnesium sulfate. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-2:1) to afford 4-fluorophenyl-1-iodopropane (7.12 g, 86% yield) as a yellow oil. washed with 10% hydrochloric acid and subsequently with a saturated aqueous sodium chloride solution dried over magnesium sulfate The solvent was evaporated in vacuo the residue was dissolved in acetone (100 ml) by stirring under a nitrogen atmosphere for 2 hours at 50° C washed with 10% aqueous sodium thiosulfate solution and subsequently with a saturated aqueous sodium chloride solution dried over magnesium sulfate The solvent was evaporated in vacuo the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-2:1)

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

Procedure: This ester (6.52 g, 33.6 mmol) was dissolved in ethyl acetate (100 ml), and 5% rhodium/alumina (1.30 g) was added thereto followed by stirring under a hydrogen atmosphere for 8 hours at room temperature. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure, and then the residue was dissolved in anhydrous tetrahydrofuran (30 ml). This solution was added dropwise to a suspension of lithium aluminium hydride (1.26 g, 33.2 mmol) in anhydrous tetrahydrofuran (60 ml) in the ice bath. The reaction mixture was stirred for 30 minutes at the same temperature, and a saturated aqueous sodium sulfate solution was added thereto followed by stirring for 10 minutes at room temperature. The mixture was filtered through Celite, and the filtrate was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-1:1) to give 4-fluorophenylpropan-1-ol (4.86 g, 95% yield) as a colorless oil. The reaction mixture was filtered through Celite the filtrate was concentrated under reduced pressure the residue was dissolved in anhydrous tetrahydrofuran (30 ml) The reaction mixture was stirred for 30 minutes at the same temperature by stirring for 10 minutes at room temperature The mixture was filtered through Celite the filtrate was extracted with ethyl acetate The organic layer was washed with a saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate The solvent was evaporated in vacuo the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-1:1)

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

Procedure: This ester (6.52 g, 33.6 mmol) was dissolved in ethyl acetate (100 ml), and 5% rhodium/alumina (1.30 g) was added thereto followed by stirring under a hydrogen atmosphere for 8 hours at room temperature. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure, and then the residue was dissolved in anhydrous tetrahydrofuran (30 ml). This solution was added dropwise to a suspension of lithium aluminium hydride (1.26 g, 33.2 mmol) in anhydrous tetrahydrofuran (60 ml) in the ice bath. The reaction mixture was stirred for 30 minutes at the same temperature, and a saturated aqueous sodium sulfate solution was added thereto followed by stirring for 10 minutes at room temperature. The mixture was filtered through Celite, and the filtrate was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-1:1) to give 4-fluorophenylpropan-1-ol (4.86 g, 95% yield) as a colorless oil. The reaction mixture was filtered through Celite the filtrate was concentrated under reduced pressure the residue was dissolved in anhydrous tetrahydrofuran (30 ml) The reaction mixture was stirred for 30 minutes at the same temperature by stirring for 10 minutes at room temperature The mixture was filtered through Celite the filtrate was extracted with ethyl acetate The organic layer was washed with a saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate The solvent was evaporated in vacuo the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-1:1)

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

Procedure: To a solution of 2.26 g (14.65 mmol) of 3-(4-fluorophenyl propanol and 3.6 mL (44 mmol) of pyridine in 40 mL of CH2Cl2 at 0° C. was added 5.1 g (29.3 mmol) of methanesulfonic anhydride and the reaction mixture was sitirred for 4 h at rt. The reaction mixture was partitioned between 100 mL of CH2Cl2 and 20 of sat'd NaHCO3 solution. The organic fraction was washed 3 times with sat'd NaHCO3 solution and sat'd NaCl solution, dried over MgSO4 and the filtrate was concentrated several times from heptane to remove pyridine. To the residue in 50 mL of acetone was added 6 g (44 mmol) of LiI and the reaction mixture was Stirred for 20 hr. The reaction mixture was poured into 200 mL of H2O and extracted with ether. The combined organic fractions were washed with sat'd NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated. The residue was purified by chromatography (silica, hexanes: ethyl acetate, 9:1) to give 3.25 g of the title compound. The reaction mixture was partitioned between 100 mL of CH2Cl2 and 20 of sat'd NaHCO3 solution The organic fraction was washed 3 times with sat'd NaHCO3 solution dried over MgSO4 the filtrate was concentrated several times from heptane to remove pyridine extracted with ether The combined organic fractions were washed with sat'd NaCl solution dried over MgSO4 filtered the filtrate was concentrated The residue was purified by chromatography (silica, hexanes: ethyl acetate, 9:1)

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

Procedure: To a solution of 2.26 g (14.65 mmol) of 3-(4-fluorophenyl propanol and 3.6 mL (44 mmol) of pyridine in 40 mL of CH2Cl2 at 0° C. was added 5.1 g (29.3 mmol) of methanesulfonic anhydride and the reaction mixture was sitirred for 4 h at rt. The reaction mixture was partitioned between 100 mL of CH2Cl2 and 20 of sat'd NaHCO3 solution. The organic fraction was washed 3 times with sat'd NaHCO3 solution and sat'd NaCl solution, dried over MgSO4 and the filtrate was concentrated several times from heptane to remove pyridine. To the residue in 50 mL of acetone was added 6 g (44 mmol) of LiI and the reaction mixture was Stirred for 20 hr. The reaction mixture was poured into 200 mL of H2O and extracted with ether. The combined organic fractions were washed with sat'd NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated. The residue was purified by chromatography (silica, hexanes: ethyl acetate, 9:1) to give 3.25 g of the title compound. The reaction mixture was partitioned between 100 mL of CH2Cl2 and 20 of sat'd NaHCO3 solution The organic fraction was washed 3 times with sat'd NaHCO3 solution dried over MgSO4 the filtrate was concentrated several times from heptane to remove pyridine extracted with ether The combined organic fractions were washed with sat'd NaCl solution dried over MgSO4 filtered the filtrate was concentrated The residue was purified by chromatography (silica, hexanes: ethyl acetate, 9:1)

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

Procedure: The obtained 4-fluorophenylpropan-1-ol (4.83 g, 31.3 mmol) was dissolved in dichloromethane (50 ml), and triethylamine (6.55 ml, 47.0 mmol) and methanesulfonyl chloride (2.91 ml, 37.6 mmol) were added thereto in the ice bath followed by stirring under a nitrogen atmosphere for 30 minutes. The reaction mixture was diluted with dichloromethane (50 ml), and washed with 10% hydrochloric acid and subsequently with a saturated aqueous sodium chloride solution, and then dried over magnesium sulfate. The solvent was evaporated in vacuo, and the residue was dissolved in acetone (100 ml), and then sodium iodide (9.39 g, 62.6 mmol) was added thereto followed by stirring under a nitrogen atmosphere for 2 hours at 50° C. The reaction mixture was diluted with ethyl acetate (250 ml), and washed with 10% aqueous sodium thiosulfate solution and subsequently with a saturated aqueous sodium chloride solution, and then dried over magnesium sulfate. The solvent was evaporated in vacua, and the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5 :1-2:1) to afford 4-fluorophenyl-1-iodopropane (7.12 g, 86% yield) as a yellow oil. washed with 10% hydrochloric acid and subsequently with a saturated aqueous sodium chloride solution dried over magnesium sulfate The solvent was evaporated in vacuo the residue was dissolved in acetone (100 ml) by stirring under a nitrogen atmosphere for 2 hours at 50° C washed with 10% aqueous sodium thiosulfate solution and subsequently with a saturated aqueous sodium chloride solution dried over magnesium sulfate The solvent was evaporated in vacua the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5 :1-2:1)

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

Procedure: This ester (6.52 g, 33.6 mmol) was dissolved in ethyl acetate (100 ml), and 5% rhodium/alumina (1.30 g) was added thereto followed by stirring under a hydrogen atmosphere for 8 hours at room temperature. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure, and then the residue was dissolved in anhydrous tetrahydrofuran (30 ml). This solution was added dropwise to a suspension of lithium aluminium hydride (126 g, 33.2 mmol) in anhydrous tetrahydrofuran (60 ml) in the ice bath. The reaction mixture was stirred for 30 minutes at the same temperature, and a saturated aqueous sodium sulfate solution was added thereto followed by stirring for 10 minutes at room temperature. The mixture was filtered through Celite, and the filtrate was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-1:1) to give 4-fluorophenylpropan-1-ol (4.86 g, 95% yield) as a colorless oil. The reaction mixture was filtered through Celite the filtrate was concentrated under reduced pressure the residue was dissolved in anhydrous tetrahydrofuran (30 ml) The reaction mixture was stirred for 30 minutes at the same temperature by stirring for 10 minutes at room temperature The mixture was filtered through Celite the filtrate was extracted with ethyl acetate The organic layer was washed with a saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate The solvent was evaporated in vacuo the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-1:1)

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

Procedure: The obtained 4-fluorophenylpropan-1-ol (4.83 g, 31.3 mmol) was dissolved in dichloromethane (50 ml), and triethylamine (6.55 ml, 47.0 mmol) and methanesulfonyl chloride (2.91 ml, 37.6 mmol) were added thereto in the ice bath followed by stirring under a nitrogen atmosphere for 30 minutes. The reaction mixture was diluted with dichloromethane (50 ml), and washed with 10% hydrochloric acid and subsequently with a saturated aqueous sodium chloride solution, and then dried over magnesium sulfate. The solvent was evaporated in vacuo, and the residue was dissolved in acetone (100 ml), and then sodium iodide (9.39 g, 62.6 mmol) was added thereto followed by stirring under a nitrogen atmosphere for 2 hours at 50° C. The reaction mixture was diluted with ethyl acetate (250 ml), and washed with 10% aqueous sodium thiosulfate solution and subsequently with a saturated aqueous sodium chloride solution, and then dried over magnesium sulfate. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-2:1) to afford 4-fluorophenyl-1-iodopropane (7.12 g, 86% yield) as a yellow oil. washed with 10% hydrochloric acid and subsequently with a saturated aqueous sodium chloride solution dried over magnesium sulfate The solvent was evaporated in vacuo the residue was dissolved in acetone (100 ml) by stirring under a nitrogen atmosphere for 2 hours at 50° C washed with 10% aqueous sodium thiosulfate solution and subsequently with a saturated aqueous sodium chloride solution dried over magnesium sulfate The solvent was evaporated in vacuo the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-2:1)

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

Procedure: This ester (6.52 g, 33.6 mmol) was dissolved in ethyl acetate (100 ml), and 5% rhodium/alumina (1.30 g) was added thereto followed by stirring under a hydrogen atmosphere for 8 hours at room temperature. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure, and then the residue was dissolved in anhydrous tetrahydrofuran (30 ml). This solution was added dropwise to a suspension of lithium aluminium hydride (1.26 g, 33.2 mmol) in anhydrous tetrahydrofuran (60 ml) in the ice bath. The reaction mixture was stirred for 30 minutes at the same temperature, and a saturated aqueous sodium sulfate solution was added thereto followed by stirring for 10 minutes at room temperature. The mixture was filtered through Celite, and the filtrate was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-1:1) to give 4-fluorophenylpropan-1-ol (4.86 g, 95% yield) as a colorless oil. The reaction mixture was filtered through Celite the filtrate was concentrated under reduced pressure the residue was dissolved in anhydrous tetrahydrofuran (30 ml) The reaction mixture was stirred for 30 minutes at the same temperature by stirring for 10 minutes at room temperature The mixture was filtered through Celite the filtrate was extracted with ethyl acetate The organic layer was washed with a saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate The solvent was evaporated in vacuo the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=5:1-1:1)

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

Procedure: To a solution of 2.26 g (14.65 mmol) of 3-(4-fluorophenyl propanol and 3.6 mL (44 mmol) of pyridine in 40 mL of CH2Cl2 at 0° C. was added 5.1 g (29.3 mmol) of methanesulfonic anhydride and the reaction mixture was sitirred for 4 h at rt. The reaction mixture was partitioned between 100 mL of CH2Cl2 and 20 of sat'd NaHCO3 solution. The organic fraction was washed 3 times with sat'd NaHCO3 solution and sat'd NaCl solution, dried over MgSO4 and the filtrate was concentrated several times from heptane to remove pyridine. To the residue in 50 mL of acetone was added 6 g (44 mmol) of LiI and the reaction mixture was Stirred for 20 hr. The reaction mixture was poured into 200 mL of H2O and extracted with ether. The combined organic fractions were washed with sat'd NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated. The residue was purified by chromatography (silica, hexanes: ethyl acetate, 9:1) to give 3.25 g of the title compound. The reaction mixture was partitioned between 100 mL of CH2Cl2 and 20 of sat'd NaHCO3 solution The organic fraction was washed 3 times with sat'd NaHCO3 solution dried over MgSO4 the filtrate was concentrated several times from heptane to remove pyridine extracted with ether The combined organic fractions were washed with sat'd NaCl solution dried over MgSO4 filtered the filtrate was concentrated The residue was purified by chromatography (silica, hexanes: ethyl acetate, 9:1)