4-benzylphenol

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:

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

Procedure: 28.2 g of 2-chloroethyl-ethyl ether is added dropwise in the course of one hour at a bath temperature of 105°-110°C, with stirring, to a mixture of 36.8 g of 4-benzylphenol, 40 g of finely pulverised anhydrous potassium carbonate, 0.5 g of potassium iodide, 0.1 g of hydroquinone, 90 ml of hexamethylphosphoric acid triamide and 90 ml of dimethylformamide; and the mixture is held for a further 20 hours at this temperature. In further processing, the cooled reaction mixture is poured into about 800 ml of ice water, and extraction is repeatedly performed with ether. The combined ether phases are washed neutral with 10% potassium hydroxide solution followed by saturated sodium chloride solution; they are then dried over sodium sulphate and treated with active charcoal. After the solvent has been distilled off, the crude product is chromatographed on silica gel (eluant: diethyl ether/hexane 1:4) to yield pure 1-benzyl-4-(2-ethoxy)-ethoxybenzene (nD20 : 1.5502). In further processing, the cooled reaction mixture The combined ether phases are washed neutral with 10% potassium hydroxide solution they are then dried over sodium sulphate treated with active charcoal After the solvent has been distilled off the crude product is chromatographed on silica gel (eluant: diethyl ether/hexane 1:4)

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

Procedure: To a solution of 3-[2-(4-benzyloxyphenyl)-5-methyl-1H-pyrrol-1-yl]propan-1-ol (1.00 g, 3.11 mmol), 4-benzylphenol (572 mg, 3.11 mmol) and triphenylphosphine (1.22 g, 4.67 mmol) in toluene (2 ml) was added 1,1′-(azodicarbonyl)dipiperidine (1.18 g, 4.67 mmol) and the mixture was stirred at 80° C. for 12 hours. The reaction solution was poured into water and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate anhydride and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=30:1) to give the object compound as an oily substance. 1.21 g (yield: 79.6%) the mixture was extracted with ethyl acetate The extract was dried over magnesium sulfate anhydride the solvent was removed under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=30:1) to give the object compound as an oily substance

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

Procedure: A solution of 4-(benzyl)phenol (638 mg, 3.46 mmol), 1-bromo-2-chloroethane (2.3 mL, 27.7 mmol) and cesium carbonate (4.5 g, 27.7 mmol) in 35 mL of acetonitrile was heated at reflux for 12 hours. After cooling, water was added. The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Flash chromatography gave 734 mg of 1-(2-chloroethoxy)-4-(benzyl)benzene, 1H NMR (300 MHz, CDCl3) δ 7.29 (dd, 2H), 7.19 (dd, 1H), 7.18 (d, 2H), 7.12 (d, 2H), 6.85 (d, 2H), 4.21 (t, 2H), 3.93 (s, 2H), 3.80 (t, 2H) ppm. at reflux for 12 hours After cooling The mixture was extracted with ethyl acetate The organic layer was washed with brine dried over sodium sulfate concentrated under reduced pressure

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

Procedure: The title compound was prepared in a similar manner to Preparation 18 from (±)N-tert-butoxycarbonyl-1,2-iminoindane (2 g, 8.7 mmol), 4-benzylphenol (1.59 g, 8.7 mmol), pyridinium p-toluenesulfonate (30 mg) and chloroform (50 ml). After a reaction time of 3 h, the reaction was diluted with chloroform (50 ml) then washed sequentially with saturated aq. sodium bicarbonate, water and brine. After drying over Na2 SO4, volatiles were removed in vacuo and the residue subjected to column chromatography on neutral alumina eluting with 10% diethyl ether in hexanes to afford the title compound (1.4 g) as a foam then washed sequentially with saturated aq. sodium bicarbonate, water and brine After drying over Na2 SO4, volatiles were removed in vacuo

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

Procedure: To a solution of (S)—N-Boc-piperidine-2-ethanol (1.00 g, 4.36 mmol), 4-hydroxydiphenylmethane (0.884 g, 4.79 mmol), and triphenylphosphine (1.26 g, 4.80 mmol) in anhydrous tetrahydrofuran (40 mL) at 0° C. under an atmosphere of nitrogen was added diisopropyl azodicarboxylate (0.92 ml, 4.80 mmol), and the resulting mixture was stirred at ambient temperature for about 20 h. The clear, yellow solution was concentrated in vacuo. The crude liquid was purified by silica gel flash chromatography to obtain the title compound as a clear, yellow oil (1.20 g, 70%): 1H NMR (400 MHz; CDCl3) δ 7.35 (m, 2H), 7.17 (m, 3H), 7.07 (d, 2H, J=8.8 Hz), 6.79 (d, 2H, J=8.8 Hz), 4.46 (m, 1H), 3.97 (m, 5H), 2.80 (br t, 1H, J=13.2 Hz), 2.12 (m, 1H), 1.85 (m, 1H), 1.60 (m, 5H), 1.40 (m, 10H). MS, m/z 418 (M+Na)+. The clear, yellow solution was concentrated in vacuo The crude liquid was purified by silica gel flash chromatography

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

Procedure: To a solution of (S)—N-Boc-piperidine-2-ethanol (1.00 g, 4.36 mmol), 4-hydroxydiphenylmethane (0.884 g, 4.79 mmol), and triphenylphosphine (1.26 g, 4.80 mmol) in anhydrous tetrahydrofuran (40 mL) at 0° C. under an atmosphere of nitrogen was added diisopropyl azodicarboxylate (0.92 ml, 4.80 mmol), and the resulting mixture was stirred at ambient temperature for about 20 h. The clear, yellow solution was concentrated in vacuo. The crude liquid was purified by silica gel flash chromatography to obtain the title compound as a clear, yellow oil (1.20 g, 70%): 1H NMR (400 MHz; CDCl3) δ 7.35 (m, 2H), 7.17 (m, 3H), 7.07 (d, 2H, J=8.8 Hz), 6.79 (d, 2H, J=8.8 Hz), 4.46 (m, 1H), 3.97 (m, 5H), 2.80 (br t, 1H, J=13.2 Hz), 2.12 (m, 1H), 1.85 (m, 1H), 1.60 (m, 5H), 1.40 (m, 10H). MS, m/z 418 (M+Na)+. The clear, yellow solution was concentrated in vacuo The crude liquid was purified by silica gel flash chromatography