2-(4-broMophenyl)propanenitrile

To a solution of 2-(4-bromophenyl)acetonitrile (5.0 g, 25.5 mmol) in anhydrous THF (70 mL) was cooled to 0 °C and sodium hydride (60 wt percent, 1.5 g, 38.3 mmol) added portion wise. The mixture was stirred at room temperature for 1 h. After which methyl iodide (1.8 mL, 28.1 mmol) was added and the mixture stirred for 14 h. The reaction mixture was carefully quenched with water at 0 °C and diluted with ethyl acetate (200 mL). The layers were seperated and the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and the residue purified by column chromatography (silica, 0-30percent ethyl acetate/heptane) to afford the desired product (3.8 g, 72percent) as a yellow oil: ESI MS m/z 210 [C HStep 1. 2-(4-Bromophenyl)propanenitriIe (1541) [00487] into a 100-mL round-bottom flask was added 2-(4-bromophenyl)acetonitrile (3.00 g, 15.3 mmol), tetrahydrofuran (30 mL), and sodium hydride (60percent by weight; 2.60 g, 65.0 mmol). The reaction mixture was stirred for I h at RT. The reaction mixture was cooled to 0 °C then iodomethane (0.551 g, 0.242 mL, 3.88 mmol) was added and the reaction mixture was stirred at RT for an additional 2 h. The reaction was then quenched by the addition of H2O (10 mL), and then was extracted with dichloromethane (3 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford 2-(4- bromophenyi)propanemtrile (2 g, 62percent) as a yellow solid. LCMS (ESI, m/z) 210 [M+H]Step 1: To a stirred solution of 2-(4-bromo phenyl) acetonitrile (20 g, 102.04 mmol) in dry tetrahydrofuran (200 mL) was added sodium bis(trimethylsilyl)amide (18.71 g, 102.04 mmol) at 0° C. under a nitrogen atmosphere. After stirring for 20 minutes at room temperature, methyl iodide (14.48 g, 102 mmol) was added and then stirred for 1 h at room temperature. The reaction mixture was quenched with an aqueous ammonium chloride solution and extracted with ethyl acetate (2×150 mL). The combined organic layers were washed with water (2×100 mL), a saturated aqueous sodium chloride solution (2×25 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (3-4percent ethyl acetate/hexanes) afforded 2-(4-bromo-phenyl)-propionitrile as a light yellow liquid (11.5 g, 53.6percent).In a round bottom flask, 2-(4-bromophenyl)acetonitrile (1.01 g, 5.15 mmol) was dissolved in DMF (5.15 mL). At 0°C was added 60percent sodium hydride (261 mg, 6.53 mmol, 1.27 eq) and methyl iodide (321 uL, 5.15 mmol, 1.0 eq) was added over 30 mm. After 2h stirring at RT, reaction was quenched by addition to cold water. Mixture was extracted with ethyl acetate, washed with saturated sodium chloride, dried over magnesium sulfate, filtered, evaporated. Purification by silica gel chromatography (0-50percent ethyl acetate in heptanes as eluent) yielded 2-(4-bromophenyl)propanenitrile (553.5 mg, 51.2percent yield). ‘H NMR (400 MHz, CHLOROFORM-d) ö 7.53 (d, I = 8.53 Hz, 2H), 7.25 (d, I = 8.28 Hz, 2H), 3.88 (q, I = 7.28 Hz, 1H), 1.64 (d, I = 7.28 Hz, 3H).Preparation 1 Intermediate 30; 2-(4-Bromo-phenyl)-propionitrile; An autoclave is charged with 25.0 g (128 mmol) 4-bromobenzylcyanide, 190 mL dimethylcarbonate and 0.900 g (6.51 mmol) K2CO3 and stirred for 16 h at 180 C. Then the reaction mixture is allowed to cool to r.t., the mixture is diluted with EtOAc and washed with water (1×), aq. 10% Na2S2O3 solution (1×) and brine (1×). The organic layer is dried with MgSO4 and the solvent is removed in vacuo. The residue is purified by destillation (bath temperature 204 C., head temperature 153 C.).C9H8BrN (M=210.1 g/mol)Rf (TLC): 0.25 (silica gel, CyH/EtOAc 9/1)Intermediate 31; 2-(4-Bromo-phenyl)-propylamine; A mixture of 3.00 g (14.3 mmol) To Preparation 2 2-(4-Bromophenyl)propylamine hydrochloride To a solution of 35.2 g (167.6 mmol) of material from Preparation 1 under reflux in 35.0 mL of tetrahydrofuran was added 18.4 ml (184.3 mmol) of 10M borane-dimethyl-sulfide slowly via a syringe. The solution was heated under reflux for an additional 1 hour after the addition was complete. The solution was cooled to ambient temperature and a saturated solution of hydrogen chloride in methanol was added slowly until pH 2 was achieved. The resulting slurry was concentrated in vacuo. The residue was dissolved in methanol and concentrated in vacuo twice.

Molecular Weight:210.07
XLogP3:2.8
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:208.98401
Monoisotopic Mass:208.98401
Topological Polar Surface Area:23.8
Heavy Atom Count:11
Complexity:162
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes