2-(2-bromophenyl)ethanol

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

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

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

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

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

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

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

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-bromophenylacetic acid (3.96 g, 18.42 mmol) in 60 mL of anhydrous THF was added slowly at room temperature 24.0 mL (23.95 mmol) of a 1 M solution BH3/THF. After finishing the addition of BH3/THF, the solution was stirred at room temperature for 1 h and then heated at 100° C. for 2 h. After this time, the solution was cooled to room temperature, and a mixture of THF and water (20 mL) was added. Potassium carbonate was then added, along with 60 mL of ether. The organic layer was separated from the mixture, and this layer was washed with water (60 mL), aqueous NaHCO3 (60 mL), and brine (60 mL) before it was dried over magnesium sulfate, filtered, and concentrated to give the crude product. This crude product was purified by silica gel flash chromatography eluting with hexanes and a 5 to 10% gradient of ethyl acetate to give 3.47 g (94%) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.57 (d, 1H, J=7.8 Hz), 7.31-7.21 (m, 2H), 7.14-7.08 (m, 1H), 3.90 (app. t, 2H, J=6.6, 6.9 Hz), 3.05 (app. t, 2H, J=6.6 Hz), 1.51 (bs, 1H). 13C NMR (100 MHz, CDCl3): δ 137.76, 132.95, 131.25, 128.19, 127.44, 124.67, 62.04, 39.30. Anal. Calc'd. for C8H9BrO: C, 47.79; H, 4.51. Found: C, 47.75; H, 4.50. heated at 100° C. for 2 h After this time, the solution was cooled to room temperature was added The organic layer was separated from the mixture this layer was washed with water (60 mL), aqueous NaHCO3 (60 mL), and brine (60 mL) before it was dried over magnesium sulfate filtered concentrated to give the crude product This crude product was purified by silica gel flash chromatography eluting with hexanes a 5 to 10% gradient of ethyl acetate to give 3.47 g (94%) as a colorless oil

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

Procedure: 9.8 g of 2-(2-bromophenyl)ethanol and 4.7 cm3 of pyridine are dissolved under an inert atmosphere in 200 cm3 of dichloromethane at a temperature close to 20° C. The reaction mixture is cooled to a temperature close to 0° C. and 4.55 cm3 of methanesulfonyl chloride are introduced dropwise. The stirring is continued for 72 h, during which time the medium is allowed to gradually climb back up to a temperature close to 20° C. 100 cm3 of a saturated aqueous solution of sodium hydrogen carbonate are added to the reaction mixture. Stirring is continued for 10 min. The aqueous phase is extracted with dichloromethane. The organic phases are combined, washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered then concentrated using a rotary evaporator under reduced pressure (5 kPa). The 18 g of brown oil obtained are purified by flash chromatography over silica (column: 200 g; particle size: 15-40 μm; eluent: 100% dichloromethane to 90% dichloromethane/10% ethyl acetate gradient). After concentrating the fractions under reduced pressure, 12.9 g of 2-(2-bromophenyl)ethyl methanesulfonate are obtained in the form of a colorless oil. close to 20° C The reaction mixture is cooled to a temperature close to 0° C. close to 20° C is continued for 10 min The aqueous phase is extracted with dichloromethane washed with a saturated aqueous solution of sodium chloride dried over magnesium sulfate filtered then concentrated a rotary evaporator under reduced pressure (5 kPa)

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

Procedure: Following the general procedure of EXAMPLE 45 (step 1) and making non-critical variations 2-(o-bromophenyl)-1-ethanol (XLIX, 3.3 g) is converted to ethyl 2-(5-bromoisochroman-1-yl)acetate (LXXI). Following the general procedure of EXAMPLE 45 (Step 2) and making non-critical variations ethyl 2-(5-bromoisochroman-1-yl)acetate (LXXI, 1.0 g) is hydrolyzed to the corresponding acid, 2-(5-bromoisochroman-1-yl)acetic acid (LXXII). The acid (LXXII, 740 mg) is coupled with p-methoxyphenylpiperazine (V) and the resulting amide, 1-(4-methoxyphenyl)-4-[2-(5-bromoisochroman-1-yl)]acetyl piperazine (LXXIII, 1.10 g) is reduced according to the general procedure described in EXAMPLE 50 (making non-critical variations) to give the title compound, mp 105-106°.

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

Procedure: To 550.0 g of o-bromophenethyl alcohol, while stirring, is added, dropwise, 375.0 g of phosphorus tribromide. After stirring for three hours at room temperature, the reaction mixture is heated on a steam bath for three hours and then poured into 6 kg of crushed ice. The mixture is extracted with three 600 and two 200 ml portions of ether. The ether extracts are washed, dried, concentrated, and the residue is distilled to give 531.0 g of o-bromophenethyl bromide, bp. about 86°-88° (0.9mm), nD26 1.5922. is added the reaction mixture is heated on a steam bath for three hours The mixture is extracted with three 600 and two 200 ml portions of ether The ether extracts are washed dried concentrated the residue is distilled