2-(4-bromophenoxy)acetonitrile

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

Procedure: Mix 4-bromophenol (1.4 mmol) in acetonitrile (5 ml) and water (2 ml), add K2CO3 (3 mmol) and bromoacetonitrile (1.5 mmol) at room temperature under inert atmosphere. Heat the mixture to 80° C. for 16 h. Analyze by LC/MS for final product. Evaporate the solvent and add water. Extract product with DCM (3×) and combine and evaporate organic phases to afford the title compound.

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

Procedure: To a solution of [(4-bromophenyl)oxy]acetonitrile (3.07 g; 14.5 mmol; step 1 above) in anhyd THF (10 mL) at 0° C. was added BH3.DMS (18.1 mL of a 2M solution in THF; 36.2 mmol), dropwise over 5 min. The mixture was heated under reflux for 1.5 h, cooled, and 2M HCl (ca. 50 mL) was slowly added. The acidic mixture was extracted with Et2O (×2) and the extracts set aside. NaOH pellets were added to the aqueous residue until ca. pH 14, and the whole was extracted with Et2O (×3). Combined extracts of the basic mixture were washed (brine), dried over Na2SO4, and concentrated in vacuo, affording the first batch of title compound as a pale yellow liquid. The reserved Et2O extracts (from acidic mixture) were concentrated in vacuo, the residue was heated at near reflux in 15 wt % NaOH (aq) for 15 min, cooled, and extracted with CH2Cl2 (×3). Combined organics were washed (brine) and concentrated in vacuo. The residue was slurried in 4M HCl and insoluble material was removed by filtration. The filtrate was extracted with Et2O (×2), pH was adjusted to ca. pH 14 by addition of NaOH pellets and extracted with Et2O (×5). Combined extracts from the basic mixture were washed (brine), dried over Na2SO4, filtered and concentrated in vacuo, affording a second batch of the title compound, which was combined with the first batch. LC/MS (method D) 1.15 min, m/z 216 (M+H, 79Br), 218 (M+H, 81Br). The mixture was heated under reflux for 1.5 h cooled The acidic mixture was extracted with Et2O (×2) NaOH pellets were added to the aqueous residue until ca. pH 14 the whole was extracted with Et2O (×3) Combined extracts of the basic mixture were washed (brine) dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of [(4-bromophenyl)oxy]acetonitrile (3.07 g; 14.5 mmol; step 1 above) in anhyd THF (10 mL) at 0° C. was added BH3.DMS (18.1 mL of a 2M solution in THF; 36.2 mmol), dropwise over 5 min. The mixture was heated under reflux for 1.5 h, cooled, and 2M HCl (ca. 50 mL) was slowly added. The acidic mixture was extracted with Et2O (×2) and the extracts set aside. NaOH pellets were added to the aqueous residue until ca. pH 14, and the whole was extracted with Et2O (×3). Combined extracts of the basic mixture were washed (brine), dried over Na2SO4, and concentrated in vacuo, affording the first batch of title compound as a pale yellow liquid. The reserved Et2O extracts (from acidic mixture) were concentrated in vacuo, the residue was heated at near reflux in 15 wt % NaOH (aq) for 15 min, cooled, and extracted with CH2Cl2 (×3). Combined organics were washed (brine) and concentrated in vacuo. The residue was slurried in 4M HCl and insoluble material was removed by filtration. The filtrate was extracted with Et2O (×2), pH was adjusted to ca. pH 14 by addition of NaOH pellets and extracted with Et2O (×5). Combined extracts from the basic mixture were washed (brine), dried over Na2SO4, filtered and concentrated in vacuo, affording a second batch of the title compound, which was combined with the first batch. LC/MS (method D) 1.15 min, m/z 216 (M+H, 79Br), 218 (M+H, 81Br). The mixture was heated under reflux for 1.5 h cooled The acidic mixture was extracted with Et2O (×2) NaOH pellets were added to the aqueous residue until ca. pH 14 the whole was extracted with Et2O (×3) Combined extracts of the basic mixture were washed (brine) dried over Na2SO4 concentrated in vacuo

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

Procedure: A mixture of p-bromophenol (2.61 g; 15.1 mmol), bromoacetonitrile (1.11 mL; 15.9 mmol), and Cs2CO3 (7.40 g; 22.7 mmol) in anhyd MeCN (25 mL) was heated at 80° C., under N2 overnight. The mixture was cooled, filtered through a pad of Celite and concentrated in vacuo. The residue was dissolved in a minimal amount of EtOAc/hexanes and filtered through a short pad of silica gel (EtOAc/hexanes eluent), affording the title compound as a colorless, waxy solid which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 4.75 (s, 2H), 6.88 (m, 2H), 7.46 (m, 2H). The mixture was cooled filtered through a pad of Celite concentrated in vacuo The residue was dissolved in a minimal amount of EtOAc/hexanes filtered through a short pad of silica gel (EtOAc/hexanes eluent)

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

Procedure: To a solution of [(4-bromophenyl)oxy]acetonitrile (3.07 g; 14.5 mmol; step 1 above) in anhyd THF (10 mL) at 0° C. was added BH3.DMS (18.1 mL of a 2M solution in THF; 36.2 mmol), dropwise over 5 min. The mixture was heated under reflux for 1.5 h, cooled, and 2M HCl (ca. 50 mL) was slowly added. The acidic mixture was extracted with Et2O (×2) and the extracts set aside. NaOH pellets were added to the aqueous residue until ca. pH 14, and the whole was extracted with Et2O (×3). Combined extracts of the basic mixture were washed (brine), dried over Na2SO4, and concentrated in vacuo, affording the first batch of title compound as a pale yellow liquid. The reserved Et2O extracts (from acidic mixture) were concentrated in vacuo, the residue was heated at near reflux in 15 wt % NaOH (aq) for 15 min, cooled, and extracted with CH2Cl2 (×3). Combined organics were washed (brine) and concentrated in vacuo. The residue was slurried in 4M HCl and insoluble material was removed by filtration. The filtrate was extracted with Et2O (×2), pH was adjusted to ca. pH 14 by addition of NaOH pellets and extracted with Et2O (×5). Combined extracts from the basic mixture were washed (brine), dried over Na2SO4, filtered and concentrated in vacuo, affording a second batch of the title compound, which was combined with the first batch. LC/MS (method D) 1.15 min, m/z 216 (M+H, 79Br), 218 (M+H, 81Br). The mixture was heated under reflux for 1.5 h cooled The acidic mixture was extracted with Et2O (×2) NaOH pellets were added to the aqueous residue until ca. pH 14 the whole was extracted with Et2O (×3) Combined extracts of the basic mixture were washed (brine) dried over Na2SO4 concentrated in vacuo

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

Procedure: A mixture of p-bromophenol (2.61 g; 15.1 mmol), bromoacetonitrile (1.11 mL; 15.9 mmol), and Cs2CO3 (7.40 g; 22.7 mmol) in anhyd MeCN (25 mL) was heated at 80° C., under N2 overnight. The mixture was cooled, filtered through a pad of Celite and concentrated in vacuo. The residue was dissolved in a minimal amount of EtOAc/hexanes and filtered through a short pad of silica gel (EtOAc/hexanes eluent), affording the title compound as a colorless, waxy solid which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 4.75 (s, 2H), 6.88 (m, 2H), 7.46 (m, 2H). The mixture was cooled filtered through a pad of Celite concentrated in vacuo The residue was dissolved in a minimal amount of EtOAc/hexanes filtered through a short pad of silica gel (EtOAc/hexanes eluent)

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

Procedure: Mix 4-bromophenol (1.4 mmol) in acetonitrile (5 ml) and water (2 ml), add K2CO3 (3 mmol) and bromoacetonitrile (1.5 mmol) at room temperature under inert atmosphere. Heat the mixture to 80° C. for 16 h. Analyze by LC/MS for final product. Evaporate the solvent and add water. Extract product with DCM (3×) and combine and evaporate organic phases to afford the title compound.

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

Procedure: To a solution of [(4-bromophenyl)oxy]acetonitrile (3.07 g; 14.5 mmol; step 1 above) in anhyd THF (10 mL) at 0° C. was added BH3.DMS (18.1 mL of a 2M solution in THF; 36.2 mmol), dropwise over 5 min. The mixture was heated under reflux for 1.5 h, cooled, and 2M HCl (ca. 50 mL) was slowly added. The acidic mixture was extracted with Et2O (×2) and the extracts set aside. NaOH pellets were added to the aqueous residue until ca. pH 14, and the whole was extracted with Et2O (×3). Combined extracts of the basic mixture were washed (brine), dried over Na2SO4, and concentrated in vacuo, affording the first batch of title compound as a pale yellow liquid. The reserved Et2O extracts (from acidic mixture) were concentrated in vacuo, the residue was heated at near reflux in 15 wt % NaOH (aq) for 15 min, cooled, and extracted with CH2Cl2 (×3). Combined organics were washed (brine) and concentrated in vacuo. The residue was slurried in 4M HCl and insoluble material was removed by filtration. The filtrate was extracted with Et2O (×2), pH was adjusted to ca. pH 14 by addition of NaOH pellets and extracted with Et2O (×5). Combined extracts from the basic mixture were washed (brine), dried over Na2SO4, filtered and concentrated in vacuo, affording a second batch of the title compound, which was combined with the first batch. LC/MS (method D) 1.15 min, m/z 216 (M+H, 79Br), 218 (M+H, 81Br). The mixture was heated under reflux for 1.5 h cooled The acidic mixture was extracted with Et2O (×2) NaOH pellets were added to the aqueous residue until ca. pH 14 the whole was extracted with Et2O (×3) Combined extracts of the basic mixture were washed (brine) dried over Na2SO4 concentrated in vacuo

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

Procedure: A mixture of p-bromophenol (2.61 g; 15.1 mmol), bromoacetonitrile (1.11 mL; 15.9 mmol), and Cs2CO3 (7.40 g; 22.7 mmol) in anhyd MeCN (25 mL) was heated at 80° C., under N2 overnight. The mixture was cooled, filtered through a pad of Celite and concentrated in vacuo. The residue was dissolved in a minimal amount of EtOAc/hexanes and filtered through a short pad of silica gel (EtOAc/hexanes eluent), affording the title compound as a colorless, waxy solid which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 4.75 (s, 2H), 6.88 (m, 2H), 7.46 (m, 2H). The mixture was cooled filtered through a pad of Celite concentrated in vacuo The residue was dissolved in a minimal amount of EtOAc/hexanes filtered through a short pad of silica gel (EtOAc/hexanes eluent)