2-(2-phenylethoxy)ethanol

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

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

Procedure: To 2-(2-phenylethoxy)-1-ethanol (0.25 g; 1.5 mmol) [J. Med. Chem., 1570 (1983)] dissolved in DMSO/CH2Cl2 (4 ml/2 ml) is added Et3N (1 ml; 7 mmol) followed by sulfur trioxide pyridine complex (1.2 g; 7.5 mmol). After 10 minutes, the reaction mixture is then diluted with Et2O and washed with brine, 1N HCl, NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo to dryness. The residue is purified by column chromatography using CH2Cl2 to obtain 2-phenylethoxyacetaldehyde which is used directly in Step B. washed with brine, 1N HCl, NaHCO3 and brine dried (MgSO4) concentrated in vacuo to dryness The residue is purified by column chromatography

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

Procedure: To 2-(2-phenylethoxy)-1-ethanol (0.25 g; 1.5 mmol) [J. Med. Chem., 1570 (1983)] dissolved in DMSO/CH2Cl2 (4 ml/2 ml) is added Et3N (1 ml; 7 mmol) followed by sulfur trioxide pyridine complex (1.2 g; 7.5 mmol). After 10 minutes, the reaction mixture is then diluted with Et2O and washed with brine, 1N HCl, NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo to dryness. The residue is purified by column chromatography using CH2Cl2 to obtain 2-phenylethoxyacetaldehyde which is used directly in Step B. washed with brine, 1N HCl, NaHCO3 and brine dried (MgSO4) concentrated in vacuo to dryness The residue is purified by column chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, at 0° C., to a stirring mixture of LiAlH4 (0.93 g, 24.63 mmol) in dry Et2O (60 mL), 2-phenethyloxyacetic acid (1.1 g, 6.15 mmol) in dry Et2O (6 mL) was added dropwise. The mixture was left to react at rt for 4 h, then at 0° C. H2O (0.93 mL), 3.0 M KOH solution (0.93 mL) and H2O (3.12 mL) were very slowly added. The mixture was stirred at 0° C. for 1 h, filtered to remove the solid residue, and the organic phase dried over Na2SO4. The organic solution was again filtered and concentrated to dryness. The crude mixture was purified by column chromatography using a Teledyne ISCO apparatus, eluting with Cy:EtOAc (from 100:0 to 60:40) affording the title compound (0.69 g, 68%) as a colorless oil. 1H NMR (DMSO-d6): δ 2.81 (t, J=7.1 Hz, 2H), 3.40-3.44 (m, 2H), 3.45-3.51 (m, 2H), 3.60 (t, J=7.1 Hz, 2H), 4.55 (t, J=5.4 Hz, 1H), 7.15-7.30 (m, 5H). was added dropwise The mixture was left to react at rt for 4 h at 0° C filtered to remove the solid residue the organic phase dried over Na2SO4 The organic solution was again filtered concentrated to dryness The crude mixture was purified by column chromatography eluting with Cy

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, at 0° C., to a stirring mixture of LiAlH4 (0.93 g, 24.63 mmol) in dry Et2O (60 mL), 2-phenethyloxyacetic acid (1.1 g, 6.15 mmol) in dry Et2O (6 mL) was added dropwise. The mixture was left to react at rt for 4 h, then at 0° C. H2O (0.93 mL), 3.0 M KOH solution (0.93 mL) and H2O (3.12 mL) were very slowly added. The mixture was stirred at 0° C. for 1 h, filtered to remove the solid residue, and the organic phase dried over Na2SO4. The organic solution was again filtered and concentrated to dryness. The crude mixture was purified by column chromatography using a Teledyne ISCO apparatus, eluting with Cy:EtOAc (from 100:0 to 60:40) affording the title compound (0.69 g, 68%) as a colorless oil. 1H NMR (DMSO-d6): δ 2.81 (t, J=7.1 Hz, 2H), 3.40-3.44 (m, 2H), 3.45-3.51 (m, 2H), 3.60 (t, J=7.1 Hz, 2H), 4.55 (t, J=5.4 Hz, 1H), 7.15-7.30 (m, 5H). was added dropwise The mixture was left to react at rt for 4 h at 0° C filtered to remove the solid residue the organic phase dried over Na2SO4 The organic solution was again filtered concentrated to dryness The crude mixture was purified by column chromatography eluting with Cy

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

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

Procedure: To 2-(2-phenylethoxy)-1-ethanol (0.25 g; 1.5 mmol) [J. Med. Chem., 1570 (1983)] dissolved in DMSO/CH2Cl2 (4 ml/2 ml) is added Et3N (1 ml; 7 mmol) followed by sulfur trioxide pyridine complex (1.2 g; 7.5 mmol). After 10 minutes, the reaction mixture is then diluted with Et2O and washed with brine, 1N HCl, NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo to dryness. The residue is purified by column chromatography using CH2Cl2 to obtain 2-phenylethoxyacetaldehyde which is used directly in Step B. washed with brine, 1N HCl, NaHCO3 and brine dried (MgSO4) concentrated in vacuo to dryness The residue is purified by column chromatography

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

Procedure: To 2-(2-phenylethoxy)-1-ethanol (0.25 g; 1.5 mmol) [J. Med. Chem., 1570 (1983)] dissolved in DMSO/CH2Cl2 (4 ml/2 ml) is added Et3N (1 ml; 7 mmol) followed by sulfur trioxide pyridine complex (1.2 g; 7.5 mmol). After 10 minutes, the reaction mixture is then diluted with Et2O and washed with brine, 1N HCl, NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo to dryness. The residue is purified by column chromatography using CH2Cl2 to obtain 2-phenylethoxyacetaldehyde which is used directly in Step B. washed with brine, 1N HCl, NaHCO3 and brine dried (MgSO4) concentrated in vacuo to dryness The residue is purified by column chromatography

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

Procedure: To 2-(2-phenylethoxy)-1-ethanol (0.25 g; 1.5 mmol) [J. Med. Chem., 1570 (1983)] dissolved in DMSO/CH2Cl2 (4 ml/2 ml) is added Et3N (1 ml; 7 mmol) followed by sulfur trioxide pyridine complex (1.2 g; 7.5 mmol). After 10 minutes, the reaction mixture is then diluted with Et2O and washed with brine, 1N HCl, NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo to dryness. The residue is purified by column chromatography using CH2Cl2 to obtain 2-phenylethoxyacetaldehyde which is used directly in Step B. washed with brine, 1N HCl, NaHCO3 and brine dried (MgSO4) concentrated in vacuo to dryness The residue is purified by column chromatography

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

Procedure: The 2-(2-phenylethoxy)ethanol obtained according to the preceding paragraph was dissolved in 100 ml of pyridine. The solution was treated with 4.48 g of methanesulfonyl chloride and the mixture was stirred at room temperature for 0.5 hour. The solvent was removed by evaporation and the residue was partitioned between ethyl acetate and 2N hydrochloric acid. The organic phase was washed with water, dried over sodium sulfate, filtered and evaporated to give 8.1 g (85%) of 2-(2-phenylethoxy)ethyl methanesulfonate in the form of an oil which was homogeneous according to chromatography. The solvent was removed by evaporation the residue was partitioned between ethyl acetate and 2N hydrochloric acid The organic phase was washed with water dried over sodium sulfate filtered evaporated

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

Procedure: () The 2-phenylethoxyacetic acid obtained according to the preceding paragraph was dissoled in 50 ml of tetrahydrofuran and the solution was added dropwise over a period of 10 minutes to a stirred suspension, cooled in an ice-bath, of 1.62 g of lithium aluminum hydride in 50 ml of tetrahydrofuran. The mixture was stirred at room temperature for 0.5 hour. The excess lithium aluminum hydride was destroyed by the addition of 1.6 ml of water, then 1.6 ml of 15% aqueous sodium hydroxide solution and finally 5 ml of water. The inorganic solids were removed by filtration, washed well with diethyl ether and the filtrates were evaporated to give 6.50 g (92%) of 2-(2-phenylethoxy)ethanol in the form of an oil which was homogenous according to chromatography. This product can be distilled under reduced pressure; boiling point 140°-142° C./15 mm Hg. the solution was added dropwise over a period of 10 minutes to a stirred suspension The excess lithium aluminum hydride was destroyed by the addition of 1.6 ml of water The inorganic solids were removed by filtration washed well with diethyl ether the filtrates were evaporated

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

Procedure: To 2-(2-phenylethoxy)-1-ethanol (0.25 g; 1.5 mmol) [J. Med. Chem., 1570 (1983)] dissolved in DMSO/CH2Cl2 (4 ml/2 ml) is added Et3N (1 ml; 7 mmol) followed by sulfur trioxide pyridine complex (1.2 g; 7.5 mmol). After 10 minutes, the reaction mixture is then diluted with Et2O and washed with brine, 1N HCl, NaHCO3 and brine, dried (MgSO4) and concentrated in yacuo to dryness. The residue is purified by column chromatography using CH2Cl2 to obtain 2-phenylethoxyacetaldehyde which is used directly in Step B. washed with brine, 1N HCl, NaHCO3 and brine dried (MgSO4) concentrated in yacuo to dryness The residue is purified by column chromatography