2-(3-bromo-5-methoxyphenyl)acetonitrile

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

Procedure: A mixture of 5-bromo-3-methoxyphenylacetonitrile (22.6 g, 0.1 m) and 10% aqueous sodium hydroxide (300 ml) in ethanol (225 ml) is heated to 95° for 18 hours. The mixture is concentrated in vacuo, acidified with 10% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate extract is washed, dried with sodium sulfate and concentrated in vacuo to give 5-bromo-3-methoxyphenylacetic acid. is heated to 95° for 18 hours The mixture is concentrated in vacuo extracted with ethyl acetate The ethyl acetate extract is washed dried with sodium sulfate concentrated in vacuo

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

Procedure: A mixture of 5-bromo-3-methoxyphenylacetonitrile (22.6 g, 0.1 m) and 10% aqueous sodium hydroxide (300 ml) in ethanol (225 ml) is heated to 95° for 18 hours. The mixture is concentrated in vacuo, acidified with 10% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate extract is washed, dried with sodium sulfate and concentrated in vacuo to give 5-bromo-3-methoxyphenylacetic acid. is heated to 95° for 18 hours The mixture is concentrated in vacuo extracted with ethyl acetate The ethyl acetate extract is washed dried with sodium sulfate concentrated in vacuo

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

Procedure: A mixture of the crude benzyl bromide and sodium cyanide (4.9 g, 0.1 m) in ethanol (500 ml) is stirred at 65° for 16 hours. The mixture is cooled, filtered and concentrated in vacuo. The residue is partitioned between water and chloroform and the chloroform phase is washed, dried with sodium sulfate and concentrated in vacuo to afford 5-bromo-3-methoxyphenylacetonitrile. The mixture is cooled filtered concentrated in vacuo The residue is partitioned between water and chloroform the chloroform phase is washed dried with sodium sulfate concentrated in vacuo

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

Procedure: A mixture of the crude benzyl bromide and sodium cyanide (4.9 g, 0.1 m) in ethanol (500 ml) is stirred at 65° for 16 hours. The mixture is cooled, filtered and concentrated in vacuo. The residue is partitioned between water and chloroform and the chloroform phase is washed, dried with sodium sulfate and concentrated in vacuo to afford 5-bromo-3-methoxyphenylacetonitrile. The mixture is cooled filtered concentrated in vacuo The residue is partitioned between water and chloroform the chloroform phase is washed dried with sodium sulfate concentrated in vacuo

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

Procedure: A borane-tetrahydrofuran complex (1 M, 73.6 mL) was added to a THF (36.8 mL) solution of Intermediate 3 at room temperature and the resulting mixture was stirred to reflux at 80° C. for 2 hours. Methanol (26 mL) and 1 N hydrochloric acid (26 mL) were added to the reaction mixture solution and the resulting mixture was stirred at room temperature for 1 hour. The resulting mixture was neutralized with 1 N aqueous sodium hydroxide solution followed by the addition of ethyl acetate (100 mL) to extract the reaction mixture, the organic layer was dried, and then the solvent was evaporated under reduced pressure to give the title compound (8.76 g). the resulting mixture was stirred at room temperature for 1 hour to extract the reaction mixture the organic layer was dried the solvent was evaporated under reduced pressure

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium cyanide (3.4 g; WAKO) was added to a DMSO (100 mL) solution of Intermediate 2 (16.3 g) at room temperature and the resulting mixture was stirred at 40° C. for 1 hour and 40 minutes. Ethyl acetate (300 mL) and saturated aqueous sodium bicarbonate solution (150 mL), and water (150 mL) were added to extract the reaction mixture, the reaction mixture was washed with saturated brine (300 mL), the organic layer was dried, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Yamazen; n-hexane/ethyl acetate) to give the title compound (11.37 g). to extract the reaction mixture the reaction mixture was washed with saturated brine (300 mL) the organic layer was dried the solvent was evaporated under reduced pressure The residue was purified by column chromatography (Yamazen; n-hexane/ethyl acetate)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product of step (iv) (4.5 g), in glacial acetic acid (30 ml) was treated with 48% aqueous HBr (30 ml) and heated at 100° C. for 24 h. The reaction mixture was partitioned between water and ethyl acetate, the organics were separated then dried (MgSO4) and evaporated under reduced pressure to give a tan solid which was triturated with ether/isohexane (4.24 g). The reaction mixture was partitioned between water and ethyl acetate the organics were separated then dried (MgSO4) evaporated under reduced pressure to give a tan solid which was triturated with ether/isohexane (4.24 g)

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

Procedure: The product from step (iii) (5.38 g) was dissolved in dry DCM (50 ml) and dry DMF (2.3 ml) added followed by thionyl chloride (2.17 ml). The reaction mixture was stirred at RT overnight, and then diluted with aqueous sodium hydrogen carbonate, extracted with DCM, dried (MgSO4) and evaporated under reduced pressure to give an oil. The oil was dissolved in DMF (20 ml), sodium cyanide (1.30 g) was added and stirred at RT overnight. The reaction mixture was diluted with water, extracted with ether, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography (eluent 1:2 ether/isohexane) to give the subtitle compound (4.50 g). extracted with DCM dried (MgSO4) evaporated under reduced pressure to give an oil stirred at RT overnight extracted with ether dried (MgSO4) evaporated under reduced pressure The residue was purified by flash column chromatography (eluent 1:2 ether/isohexane)

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

Procedure: A mixture of 5-bromo-3-methoxyphenylacetonitrile (22.6 g, 0.1 m) and 10% aqueous sodium hydroxide (300 ml) in ethanol (225 ml) is heated to 95° for 18 hours. The mixture is concentrated in vacuo, acidified with 10% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate extract is washed, dried with sodium sulfate and concentrated in vacuo to give 5-bromo-3-methoxyphenylacetic acid. is heated to 95° for 18 hours The mixture is concentrated in vacuo extracted with ethyl acetate The ethyl acetate extract is washed dried with sodium sulfate concentrated in vacuo

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

Procedure: A mixture of 5-bromo-3-methoxyphenylacetonitrile (22.6 g, 0.1 m) and 10% aqueous sodium hydroxide (300 ml) in ethanol (225 ml) is heated to 95° for 18 hours. The mixture is concentrated in vacuo, acidified with 10% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate extract is washed, dried with sodium sulfate and concentrated in vacuo to give 5-bromo-3-methoxyphenylacetic acid. is heated to 95° for 18 hours The mixture is concentrated in vacuo extracted with ethyl acetate The ethyl acetate extract is washed dried with sodium sulfate concentrated in vacuo

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

Procedure: A mixture of the crude benzyl bromide and sodium cyanide (4.9 g, 0.1 m) in ethanol (500 ml) is stirred at 65° for 16 hours. The mixture is cooled, filtered and concentrated in vacuo. The residue is partitioned between water and chloroform and the chloroform phase is washed, dried with sodium sulfate and concentrated in vacuo to afford 5-bromo-3-methoxyphenylacetonitrile. The mixture is cooled filtered concentrated in vacuo The residue is partitioned between water and chloroform the chloroform phase is washed dried with sodium sulfate concentrated in vacuo