3-(4-bromophenyl)propan-1-ol

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 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (100 mg, 0.379 mmol) in dioxane (2 mL) and DMF (0.1 mL) was added N,N-dimethylformiminium chloride (180 mg, 0.36 mmol). The resulting mixture was stirred at room temperature for 20 min. The reaction was quenched with 2.0N potassium carbonate (1.5 mL, 3.0 mmol), then 3-(4-bromophenyl)propan-1-ol (81.5 mg, 0.379 mmol) and Pd(dppf)Cl2 (28 mg, 0.037 mmol) were added, then heated to 90° C. for 30 min. The reaction mixture was extracted with EtOAc (3 mL×3), combined the organic layers and concentrated in vacuo to afford the title compound (40 mg, 27% yield) after purification via preparative TLC. heated to 90° C. for 30 min The reaction mixture was extracted with EtOAc (3 mL×3) concentrated in vacuo

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

Procedure: Compound 41-2 (3.63 g) was dissolved in methylene chloride (40 ml), triphenylphosphine (4.88 g) and N-bromosuccinimide (3.31 g) were added under ice-cooling, and the mixture was stirred under ice-cooling for 2 hr, and at room temperature for 4 hr. The reaction mixture was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Diethyl ether (100 ml) was added, and the precipitated triphenylphosphine oxide was filtered off. The concentrate of the filtrate was purified by silica gel column chromatography (hexane alone) to give the object product (1.87 g) as a colorless oil. cooling cooling for 2 hr The reaction mixture was washed with water and saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure Diethyl ether (100 ml) was added the precipitated triphenylphosphine oxide was filtered off The concentrate of the filtrate was purified by silica gel column chromatography (hexane alone)

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

Procedure: To a solution of 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (100 mg, 0.379 mmol) in dioxane (2 mL) and DMF (0.1 mL) was added N,N-dimethylformiminium chloride (180 mg, 0.36 mmol). The resulting mixture was stirred at room temperature for 20 min. The reaction was quenched with 2.0 N potassium carbonate (1.5 mL, 3.0 mmol), then 3-(4-bromophenyl)propan-1-ol (81.5 mg, 0.379 mmol) and Pd(dppf)Cl2 (28 mg, 0.037 mmol) were added, then heated to 90° C. for 30 min. The reaction mixture was extracted with EtOAc (3 mL×3), combined the organic layers and concentrated in vacuo to afford the title compound (40 mg, 27% yield) after purification via preparative TLC. heated to 90° C. for 30 min The reaction mixture was extracted with EtOAc (3 mL×3) concentrated in vacuo

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

Procedure: To a solution under inert gas of 36.4 g of 3-(4-bromophenyl)-2-propynol (stage A) in 200 ml of ethanol at 5% of toluene, is added 200 ml of toluene, 7.9 g of Wilkinson's reagent and hydrogen at 1900 mbar for 5 hours. It is evaporated at reduced pressure until the obtainment of 45.9 g of raw product that is purified by chromatography on silica by eluting with the compound CH2Cl2/AcOEt 95/5. 30.1 g of expected product is obtained. It is evaporated at reduced pressure until the obtainment of 45.9 g of raw product that is purified by chromatography on silica by eluting with the compound CH2Cl2/AcOEt 95/5

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

Procedure: A mixture of 4-bromobenzenepropanol (9.0 g), cuprous cyanide (4.5 g), cuprous iodide (20 mg), and N-methyl-2-pyrrolidone (20 ml) was heated at 180°-190° for 4 h and poured into a solution of ferric chloride hexahydrate (4.5 g) in hydrochloric acid (2 M; 30 ml). The mixture was heated at 70°-80° for 15 min and extracted with EA (3×100 ml). The extract was washed with hydrochloric acid (2 M; 50 ml), water (50 ml), and aqueous sodium hydroxide (2 M; 50 ml), dried and evaporated. The residue was purified by [C] eluting with cyclohexane-ER (1:1) to give the title compound (3.5 g). T.l.c. (cyclohexane-ER 1:1) Rf 0.15 was heated at 180°-190° for 4 h The mixture was heated at 70°-80° for 15 min extracted with EA (3×100 ml) The extract was washed with hydrochloric acid (2 M; 50 ml), water (50 ml), and aqueous sodium hydroxide (2 M; 50 ml) dried evaporated The residue was purified by [C] eluting with cyclohexane-ER (1:1)

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

Procedure: A mixture of 4-bromobenzenepropanol (9.0 g), cuprous cyanide (4.5 g), cuprous iodide (20 mg), and N-methyl-2-pyrrolidone (20 ml) was heated at 180°-190° for 4 h and poured into a solution of ferric chloride hexahydrate (4.5 g) in hydrochloric acid (2 M; 30 ml). The mixture was heated at 70°-80° for 15 min and extracted with EA (3×100 ml). The extract was washed with hydrochloric acid (2 M; 50 ml), water (50 ml), and aqueous sodium hydroxide (2 M; 50 ml), dried and evaporated. The residue was purified by [C] eluting with cyclohexane-ER (1:1) to give the title compound (3.5 g). T.l.c. (cyclohexane-ER 1:1) Rf 0.15 was heated at 180°-190° for 4 h The mixture was heated at 70°-80° for 15 min extracted with EA (3×100 ml) The extract was washed with hydrochloric acid (2 M; 50 ml), water (50 ml), and aqueous sodium hydroxide (2 M; 50 ml) dried evaporated The residue was purified by [C] eluting with cyclohexane-ER (1:1)

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

Procedure: To 3-(4-bromophenyl)propan-1-ol (4.70 g, 21.9 mmol), isoindoline-1,3-dione (3.54 g, 24.0 mmol) and triphenylphosphine (6.88 g, 26.2 mmol) in a 500 mL round bottomed flask equipped with a stir bar, nitrogen, and addition funnel, and cooled in an ice water bath was added diisopropyl azodicarboxylate (5.10 mL, 26.2 mmol). The reaction was allowed to warm to room temperature over the weekend. The reaction mixture was adsorbed onto Celite®. Purification by flash column chromatography using 5-20% ethyl acetate/hexanes as eluent provided a solid which was dried overnight at 50° C. in vacuo to afford the title compound as a white solid (6.51 g, 87%): mp 88-90° C., 1H NMR (400 MHz, CDCl3) δ 7.86-7.79 (m, 2H), 7.71 (dd, J=5.5, 3.0 Hz, 2H), 7.38-7.32 (m, 2H), 7.11-7.04 (m, 2H), 3.73 (t, J=7.1 Hz, 2H), 2.68-2.59 (m, 2H), 2.07-1.96 (m, 2H); ESIMS m/z 346 [(M+2)+]. nitrogen, and addition funnel cooled in an ice water bath Purification by flash column chromatography provided a solid which was dried overnight at 50° C. in vacuo

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

Procedure: 3-(4-bromophenyl)propionic acid (Aldrich) (12.25 g, 53.48 mmol) was dissolved in tetrahydrofuran (100 mL) and the solution was slowly added to lithium aluminum hydride (1.22 g, 32.09 mmol) in tetrahydrofuran (100 mL). The reaction was stirred for 3 h, then 150 mL 1 N aqueous sodium hydrogen carbonate was added, the mixture was extracted with ethyl acetate (3×150 mL) and the organic phases were dried over magnesium sulphate and concentrated in vacuo. The crude product was used without purification. the mixture was extracted with ethyl acetate (3×150 mL) the organic phases were dried over magnesium sulphate concentrated in vacuo The crude product was used without purification

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

Procedure: To 3-(4-bromophenyl)propan-1-ol (4.70 g, 21.9 mmol), isoindoline-1,3-dione (3.54 g, 24.0 mmol) and triphenylphosphine (6.88 g, 26.2 mmol) in a 500 mL round bottomed flask equipped with a stir bar, nitrogen, and addition funnel, and cooled in an ice water bath was added diisopropyl azodicarboxylate (5.10 mL, 26.2 mmol). The reaction was allowed to warm to room temperature over the weekend. The reaction mixture was adsorbed onto Celite®. Purification by flash column chromatography using 5-20% ethyl acetate/hexanes as eluent provided a solid which was dried overnight at 50° C. in vacuo to afford the title compound as a white solid (6.51 g, 87%): mp 88-90° C.; 1H NMR (400 MHz, CDCl3) δ 7.86-7.79 (m, 2H), 7.71 (dd, J=5.5, 3.0 Hz, 2H), 7.38-7.32 (m, 2H), 7.11-7.04 (m, 2H), 3.73 (t, J=7.1 Hz, 2H), 2.68-2.59 (m, 2H), 2.07-1.96 (m, 2H); ESIMS m/z 346 [(M+2)+]. nitrogen, and addition funnel cooled in an ice water bath Purification by flash column chromatography provided a solid which was dried overnight at 50° C. in vacuo

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

Procedure: To a solution of 3-(4-bromophenyl)propan-1-ol (1 eq.) in DMF (0.25 M) was added imidazole (1.2 eq.) and tert-butyldimethylsilyl chloride (1.1 eq.). The resulting solution was stirred at RT for 13 h. The reaction mixture was quenched with sat. aq. NH4Cl and extracted with hexanes. The combined organic extracts were washed further with water and brine. Concentration of the organic extracts in vacuo afforded the title compound as a colorless oil. The reaction mixture was quenched with sat. aq. NH4Cl extracted with hexanes The combined organic extracts were washed further with water and brine