2-chloroethylbenzene

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: 1,2,3-Triazole (1634 mg, 23.7 mmol), sodium iodide (2364 mg, 15.8 mmol), sodium hydroxide (946 mg, 23.7 mmol) were added to t-amyl alcohol (6.2 ml), and the mixture was refluxed under stirring for 1 hour. 1-Chloro-2-phenylethane (2217 mg, 15.8 mmol) was dissolved in t-amyl alcohol (6.2 ml) and added dropwise under reflux over 1 hour. The mixture was refluxed under stirring for 3.5 hours. The mixture was cooled to room temperature and toluene (50 ml) was added. The mixture was washed with water (50×2), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1→1/3) to give 1-(2-phenylethyl)-1H-1,2,3-triazole as a colorless oil (2.0 g, yield 73%). 2-(2-Phenylethyl)-2H-1,2,3-triazole (315 mg) was obtained as a colorless oil (yield 12%). 1-(4-phenylethyl)-1H-1,2,3-triazole the mixture was refluxed added dropwise under reflux over 1 hour The mixture was refluxed under stirring for 3.5 hours The mixture was washed with water (50×2) dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1→1/3)

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

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: s-BuLi (28.0 mL, 1.3 M) was added slowly to a solution of Compound 20b (7.0 g) in THF (50 mL) at −78° C. The mixture stirred for 1 hr at −78° C. and then (2-chloro-ethyl)-benzene Compound 20c (5.11 g, 36.4 mmol) in THF (10 mL) was added dropwise. The reaction mixture was stirred for 24 hrs while warming to r.t. The reaction was quenched with 1N HCl (5 mL), then diluted with water (100 mL) and EtOAc (500 mL). The organic layer was washed with brine, separated and dried with anhydrous sodium sulfate, then filtered and concentrated in vacuo to yield a crude product. Purification by flash chromatography (eluted with 10% EtOAc in Hexane) afforded 2-phenethyl-cyclohexanone Compound 20d (4.05 g, 20.0 mMol, 58%) as a yellow oil. The reaction mixture was stirred for 24 hrs while warming to r.t The reaction was quenched with 1N HCl (5 mL) diluted with water (100 mL) and EtOAc (500 mL) The organic layer was washed with brine separated dried with anhydrous sodium sulfate filtered concentrated in vacuo to yield a crude product Purification by flash chromatography (eluted with 10% EtOAc in Hexane)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: s-BuLi (28.0 mL, 1.3 M) was added slowly to a solution of Compound 20b (7.0 g) in THF (50 mL) at −78° C. The mixture stirred for 1 hr at −78° C. and then (2-chloro-ethyl)-benzene Compound 20c (5.11 g, 36.4 mmol) in THF (10 mL) was added dropwise. The reaction mixture was stirred for 24 hrs while warming to r.t. The reaction was quenched with 1N HCl (5 mL), then diluted with water (100 mL) and EtOAc (500 mL). The organic layer was washed with brine, separated and dried with anhydrous sodium sulfate, then filtered and concentrated in vacuo to yield a crude product. Purification by flash chromatography (eluted with 10% EtOAc in Hexane) afforded 2-phenethyl-cyclohexanone Compound 20d (4.05 g, 20.0 mMol, 58%) as a yellow oil. The reaction mixture was stirred for 24 hrs while warming to r.t The reaction was quenched with 1N HCl (5 mL) diluted with water (100 mL) and EtOAc (500 mL) The organic layer was washed with brine separated dried with anhydrous sodium sulfate filtered concentrated in vacuo to yield a crude product Purification by flash chromatography (eluted with 10% EtOAc in Hexane)

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

Procedure: In a 1 L flask, solid sodium hydroxide (10.50 g, 0.263 mol) was dissolved in MeOH (150 ml), and then slowly combined with 2-mercaptoacetic acid (11.51 g, 0.125 mol). The mixture was then treated in portions with (2-chloroethyl)benzene (19.33 g, 0.138 mol), heated at reflux for 10 hours, stirred for 6 hours at ambient temperature, concentrated to dryness on a rotovap, treated with water (500 mL) and extracted with Et2O (2×150 mL). These Et2O extractions were discarded. The aqueous layer was acidified to pH ˜2 with concentrated HCl and extracted with Et2O (2×150 mL). These Et2O extractions were combined, washed with brine, dried (MgSO4), filtered and concentrated to provide the title compound. 1H NMR (CDCl3) δ 2.93 (s, 4H), 3.25 (s, 2H), 7.17-7.34 (m, 5H); MS (M+NH4)+ m/z 214. heated at reflux for 10 hours concentrated to dryness on a rotovap treated with water (500 mL) extracted with Et2O (2×150 mL) These Et2O extractions extracted with Et2O (2×150 mL) These Et2O extractions washed with brine dried (MgSO4) filtered concentrated

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

Procedure: 1-(2-phenylethyl)-4-piperidone is prepared from 4-piperidone and (2-chloroethyl)benzene essentially as described above in Example 38, Scheme C, step a.