3-(2-BROMO-PHENYL)-PROPAN-1-OL

A solution of 3-(2-bromophenyl)propanoic acid (1.0 g, 4.4 mmol) in anhydrous tetrahydrofuran (5.0 mL) was treated with borane-tetrahydrofuran complex in tetrahydrofuran (1.0 M, 7.0 mL, 7.0 mmol) at 0° C. over a period of 15 minutes. The mixture was stirred at 0° C. for an additional 1 hour. After completion, the residual borane was quenched by the cautious addition of water (1 mL) and the solvent was removed under vacuum. The resulting residue was dissolved in ether (20 mL) and the organic layer was washed with water (20 mL), brine (20 mL), dried over sodium sulfate, filtered, and concentrated under pressure to afford 3-(2-bromophenyl)propan-1-ol as a colorless oil (938 mg, quantitative yield). This compound was used in the following step without further purification3-(2-Bromophenyl)propionic acid (1.15 g, 5.0 mmol) was placed in a 100 mL three-necked flask with magnetic stirrer. The atmosphere was exchanged with N3-(2-Bromophenyl)-1-propanol C. 2-Bromobenzenepropanol To a stirring solution of 196.9 g (95% pure=187.1 g, 770 mmol) of compound B in 770 mL of toluene under argon cooled to 0 C. (ice bath), 830 mL of 1.0M diisobutylaluminum hydride (DIBAL-H) in toluene solution (830 mmol, Aldrich) was added over 45 minutes. The reaction was not very exothermic. After the mixture was stirred for 1 hour, TLC indicated approximately half of the starting material remained. Next, 580 mL of 1.5M DIBAL-H in toluene solution (870 mmol, Aldrich) was added slowly. The ice bath was removed and stirring was continued for 2 hours. The mixture was then poured slowly into 1.2 L of 6M aqueous HCl stirring in an ice bath. This quench was exothermic and gas was evolved. After the mixture was recooled to 0, the layers were separated, and the organic layer was washed with 1M aqueous HCl and brine. It was then dried over Na2 SO4 and MgSO4 and evaporated (and re-evaporated with CH2 Cl2 to drive off toluene) to obtain 173.0 g of clear, colorless oil. This oil was 95% pure title compound with 5% of dibromo title compound. The corrected yield of the title compound was 99% (164.3 g).C. 2-Bromobenzenepropanol To a stirring solution of 196.9 g (95% pure=187.1 g, 770 mmol) of Part B compound in 770 mL of toluene under argon cooled to 0 (ice bath), was added over 45 minutes 830 mL of 1.0 M diisobutylaluminum hydride (DIBAl-H) in toluene solution (830 mmol, Aldrich). The reaction was not very exothermic. After the mixture was stirred for 1 hour, TLC indicated approximately half of the starting material remained. Next, 580 mL of 1.5 M DIBAl-H in toluene solution (870 mmol, Aldrich) was added slowly. The ice bath was removed and stirring was continued for 2 hours. The mixture was then poured slowly into 1.2 L of 6 M aqueous HCl stirring in an ice bath. This quench was exothermic and gas was evolved. After the mixture was recooled to 0, the layers were separated, and the organic layer was washed with 1 M aqueous HCl and brine. It was then dried over Na2 SO4 and MgSO4 and evaporated (and re-evaporated with CH2 Cl2 to drive off toluene) to obtain 173.0 g of clear, colorless oil. This oil was 95% pure title compound with 5% of debromo- title compound. The corrected yield of title compound was 99% (164.3 g).C. 2-Bromobenzenepropanol To a solution of 13.6 g (56.0 mmol) of Part B compound in 75 mL of toluene (Burdick and Jackson, sieve-dried) cooled to -78 was added 118 mL (1.0 M in toluene, 118 mmol, Aldrich) of diisobutylaluminum hydride solution. The reaction was stirred at -78 for 2 hours then warmed to 0 for 2 hours. The resulting solution was quenched by very slow addition of 10 mL of 6 N HC1then more rapid addition of 100 mL of 6 N HC1. The reaction was stirred for an additional 10 minutes, then added to 50 mL of diethyl ether and the organic layer was separated. The organic layer was washed with two-100 mL portions of 1 N HC1, 100 mL of brine, dried (magnesium sulfate) and concentrated in vacuo to afford 12.0 g (55.8 mmol, 100%) of title compound as a colorless oil.C. 2-Bromobenzenepropanol To a stirring solution of 196.9 g (95% pure=187.1 g, 770 mmol) of Part B compound in 770 mL of toluene under argon cooled to 0 (ice bath), was added over 45 minutes 830 mL of 1.0M diisobutylaluminum hydride (DIBAl-H) in toluene solution (830 mmol, Aldrich). The reaction was not very exothermic. After the mixture was stirred for 1 hour, TLC indicated approximately half of the starting material remained. Next, 580 mL of 1.5M DIBAl-H in toluene solution (870 mmol, Aldrich) was added slowly. The ice bath was removed and stirring was continued for 2 hours. The mixture was then poured slowly into 1.2 L of 6M aqueous HCl stirring in an ice bath. This quench was exothermic and gas was evolved. After the mixture was recooled to 0, the layers were separated, and the organic layer was washed with 1M aqueous HCl and brine. It was then dried over Na2 SO4 and MgSO4 and evaporated (and re-evaporated with CH2 Cl2 to drive off toluene) to obtain 173.0 g of clear, colorless oil. This oil was 95% pure title compound with 5% of debromo- title compound. The corrected yield of title compound was 99% (164.3 g).C. 2-Bromobenzenepropanol To a stirred solution of 196.9 g (95% pure, 187.1 g, 770 mmol) of Part B compound in 770 mL of toluene under argon cooled to 0 (ice bath), was added over 45 minutes 830 mL of 1.0M diisobutylaluminum hydride (DIBAL-H) in toluene solution (830 mmol). The reaction was not very exothermic. After the mixture was stirred for 1 hour, TLC indicated approximately half of the starting material remained. Next, 580 mL of 1.5 M DIBAL-H in toluene solution (870 mmol) wa added slowly. The ice bath was removed and stirring was continued for 2 hours. The mixture was then poured slowly into 1.2 L of 6M aqueous HCl stirring in an ice bath. This quench was exothermic and gas was evolved. After the mixture was recooled to 0, the layers were separated, and the organic layer was washed with 1M aqueous HCl and brine. It was then dried over Na2 SO4 and MgSO4 and evaporated (and re-evaporated with CH2 Cl2 to drive off toluene) to obtain 173.0 g of a clear, colorless oil. This oil was 95% pure title compound with 5% of the part B title compound. The corrected yield of title compound was 99% (164.3 g).C. 2-Bromobenzenepropanol To a stirring solution of 196.9 g (95% pure=187.1 g, 770 mmol) of compound B in 770 mL of toluene under argon cooled to 0 C. (ice bath), 830 mL of 1.0 M diisobutylaluminum hydride (DIBAL-H) in toluene solution (830 mmol, Aldrich) was added over 45 minutes. The reaction was not very exothermic. After the mixture was stirred for 1 hour, TLC indicated approximately half of the starting material remained. Next, 580 mL of 1.5 M DIBAL-H in toluene solution (870 mmol, Aldrich) was added slowly. The ice bath was removed and stirring was continued for 2 hours. The mixture was then poured slowly into 1.2 L of 6 M aqueous HCl stirring in an ice bath. This quench was exothermic and gas was evolved. After the mixture was recooled to 0, the layers were separated, and the organic layer was washed with 1 M aqueous HCl and brine. It was then dried over Na2 SO4 and MgSO4 and evaporated (and re-evaporated with CH2 Cl2 to drive off toluene) to obtain 173.0 g of clear, colorless oil. This oil was 95% pure title compound with 5% of debromo title compound. The corrected yield of the title compound was 99% (164.3 g).C. 2-Bromobenzenepropanol To a stirring solution of 196.9 g (95% pure, 187.1 g, 770 mmol) of Part B compound in 770 mL of toluene under argon cooled to 0 (ice bath), was added over 45 minutes 830 mL of 1.0 M diisobutylaluminum hydride (DIBAL-H) in toluene solution (830 mmol). The reaction was not very exothermic. After the mixture was stirred for 1 hour, TLC indicated approximately half of the starting material remained. Next, 580 mL of 1.5 M DIBAL-H in toluene solution (870 mmol) was added slowly. The ice bath was removed and stirring was continued for 2 hours. The mixture was then poured slowly into 1.2 L of 6 M aqueous HCl stirring in an ice bath. This quench was exothermic and gas was evolved. After the mixture was recooled to 0, the layers were separated, and the organic layer was washed with 1M aqueous HCl and brine. It was then dried over Na2 SO4 and MgSO4 and evaporated (and re-evaporated with CH2 Cl2 to drive off toluene) to obtain 173.0 g of a clear, colorless oil. This oil was 95% pure title compound with 5% of the part B title compound. The corrected yield of title compound was 99% (164.3 g).

Molecular Weight:215.09
XLogP3:2.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:3
Exact Mass:213.99933
Monoisotopic Mass:213.99933
Topological Polar Surface Area:20.2
Heavy Atom Count:11
Complexity:106
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes