methyl 3-(4-hydroxyphenyl)-2-methoxypropanoate

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

Procedure: A solution of methyl 2-diazo-3-(4-hydroxyphenyl)propanoate (cf Tetrahedron Lett., 1971, 4495) (8.58 g) in methanol (120 mL) was added over 10 minutes to a mixture of rhodium (II) acetate dimer (0.18 g) in methanol (50 mL) at room temperature under a nitrogen atmosphere. The resulting mixture was heated at reflux for 5 hrs, allowed to stand at room temperature for 15 hrs, then concentrated in vacuo. The residue was dissolved in ethyl acetate (500 mL), washed with water (3×300 mL) and brine (500 mL), dried (MgSO4) and evaporated. The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent to afford the title compound. mp 61°-3° C. The resulting mixture was heated at reflux for 5 hrs concentrated in vacuo The residue was dissolved in ethyl acetate (500 mL) washed with water (3×300 mL) and brine (500 mL) dried (MgSO4) evaporated The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent

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

Procedure: A solution of methyl 2-diazo-3-(4-hydroxyphenyl)propanoate (cf Tetrahedron Lett., 1971, 4495) (8.58 g) in methanol (120 mL) was added over 10 minutes to a mixture of rhodium (II) acetate dimer (0.18 g) in methanol (50 mL) at room temperature under a nitrogen atmosphere. The resulting mixture was heated at reflux for 5 hrs, allowed to stand at room temperature for 15 hrs, then concentrated in vacuo. The residue was dissolved in ethyl acetate (500 mL), washed with water (3×300 mL) and brine (500 mL), dried (MgSO4) and evaporated. The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent to afford the title compound. mp 61°-3° C. The resulting mixture was heated at reflux for 5 hrs concentrated in vacuo The residue was dissolved in ethyl acetate (500 mL) washed with water (3×300 mL) and brine (500 mL) dried (MgSO4) evaporated The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent

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

Procedure: A solution of methyl 2-diazo-3-(4hydroxyphenyl)propanoate (cf Tetrahedron Lett., 1971,4495) (8.58 g) in methanol (120 mL) was added over 10 minutes to a mixture of rhodium (II) acetate dimer (0.18 g) in methanol (50 mL) at room temperature under a nitrogen atmosphere. The resulting mixture was heated at reflux for 5 hrs, allowed to stand at room temperature for 15 hrs, then concentrated in vacuo. The residue was dissolved in ethyl acetate (500 mL), washed with water (3×300 mL) and brine (500 mL), dried (MgSO4) and evaporated. The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent to afford the title compound, mp 61-3° C. The resulting mixture was heated at reflux for 5 hrs concentrated in vacuo The residue was dissolved in ethyl acetate (500 mL) washed with water (3×300 mL) and brine (500 mL) dried (MgSO4) evaporated The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent

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

Procedure: 3-(4-Hydroxyphenyl)-2-methoxypropanoic acid methyl ester was alkylated with 2-(4-methanesulfonyloxyphenyl)ethylmethanesulfonate (described in Example 1a) using the same method as in Example 1 (b) to give 3-{4-[2-(4-methanesulfonyloxyphenyl)ethoxy]-phenyl}-2-methoxypropanoic acid methyl ester.

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

Procedure: 3-(4-Benzyloxyphenyl)-2-methoxypropanoic acid methyl ester (1.91 g; 6.36 mmole) was hydrogenated in methanol (30 ml) using Pd/C (5%, wet, 0.9 g) as catalyst. The mixture was filtered through celite and the filtrate was evaporated in vacuo to give 1.16 g (yield 87%) of 3-(4-hydroxyphenyl)-2-methoxypropanoic acid methyl ester. The mixture was filtered through celite the filtrate was evaporated in vacuo

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

Procedure: A solution of methyl 2-diazo-3-(4-hydroxyphenyl)propanoate (cf Tetrahedron Lett., 1971, 4495) (8.58 g) in methanol (120 mL) was added over 10 minutes to a mixture of rhodium (II) acetate dimer (0.18 g) in methanol (50 mL) at room temperature under a nitrogen atmosphere. The resulting mixture was heated at reflux for 5 hrs, allowed to stand at room temperature for 15 hrs, then concentrated in vacuo. The residue was dissolved in ethyl acetate (500 mL), washed with water (3×300 mL) and brine (500 mL), dried (MgSO4) and evaporated. The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent to afford the title compound. mp 61°-3° C. The resulting mixture was heated at reflux for 5 hrs concentrated in vacuo The residue was dissolved in ethyl acetate (500 mL) washed with water (3×300 mL) and brine (500 mL) dried (MgSO4) evaporated The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent

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

Procedure: A solution of methyl 2-diazo-3-(4-hydroxyphenyl)propanoate (cf Tetrahedron Lett., 1971, 4495) (8.58 g) in methanol (120 mL) was added over 10 minutes to a mixture of rhodium (II) acetate dimer (0.18 g) in methanol (50 mL) at room temperature under a nitrogen atmosphere. The resulting mixture was heated at reflux for 5 hrs, allowed to stand at room temperature for 15 hrs, then concentrated in vacuo. The residue was dissolved in ethyl acetate (500 mL), washed with water (3×300 mL) and brine (500 mL), dried (MgSO4) and evaporated. The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent to afford the title compound. mp 61°-3° C. The resulting mixture was heated at reflux for 5 hrs concentrated in vacuo The residue was dissolved in ethyl acetate (500 mL) washed with water (3×300 mL) and brine (500 mL) dried (MgSO4) evaporated The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent

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

Procedure: A solution of methyl 2-diazo-3-(4-hydroxyphenyl)propanoate (cf Tetrahedron Lett., 1971, 4495) (8.58 g) in methanol (120 mL) was added over 10 minutes to a mixture of rhodium (II) acetate dimer (0.18 g) in methanol (50 mL) at room temperature under a nitrogen atmosphere. The resulting mixture was heated at reflux for 5 hrs, allowed to stand at room temperature for 15 hrs, then concentrated in vacuo. The residue was dissolved in ethyl acetate (500 mL), washed with water (3×300 mL) and brine (500 mL), dried (MgSO4) and evaporated. The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent to afford the title compound. mp 61°-3° C. The resulting mixture was heated at reflux for 5 hrs concentrated in vacuo The residue was dissolved in ethyl acetate (500 mL) washed with water (3×300 mL) and brine (500 mL) dried (MgSO4) evaporated The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent

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

Procedure: A solution of methyl 2-diazo-3-(4-hydroxyphenyl)propanoate (cf Tetrahedron Lett., 1971, 4495) (8.58 g) in methanol (120 mL) was added over 10 minutes to a mixture of rhodium (II) acetate dimer (0.18 g) in methanol (50 mL) at room temperature under a nitrogen atmosphere. The resulting mixture was heated at reflux for 5 hrs, allowed to stand at room temperature for 15 hrs, then concentrated in vacuo. The residue was dissolved in ethyl acetate (500 mL), washed with water (3×300 mL) and brine (500 mL), dried (MgSO4) and evaporated. The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent to afford the title compound. mp 61°-3° C. The resulting mixture was heated at reflux for 5 hrs concentrated in vacuo The residue was dissolved in ethyl acetate (500 mL) washed with water (3×300 mL) and brine (500 mL) dried (MgSO4) evaporated The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent

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

Procedure: Methyl 3-(4-hydroxyphenyl)-2-methoxypropanoate (132 g, 0.631 mol) was dissolved in methanol (700 mL) and 5N sodium hydroxide (631 mL, 3.16 mol) was added dropwise at ambient temperature. The solution was stirred for 16 h at ambient temperature. The methanol was removed under vacuum, and water (500 mL) was added. The mixture was extracted with MTBE (2×500 mL). The aqueous solution was brought to pH=1 with concentrated HCl and then extracted with MTBE (2×500 nL). The organic extracts were dried (MgSO4), filtered, and concentrated under vacuum to give racemic 3-(4-hydroxyphenyl)-2-methoxypropanoic acid as an oil (110 g), which crystallized upon standing. 1H-NMR (DMSO): 7.0 (d, 2H); 6.6 (d, 2H); 4.0 (m, 1H); 2.8 (m, 2H); MS (ES−) m/z 195.1 (M−1). The methanol was removed under vacuum, and water (500 mL) was added The mixture was extracted with MTBE (2×500 mL) extracted with MTBE (2×500 nL) The organic extracts were dried (MgSO4) filtered concentrated under vacuum

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

Procedure: A solution of methyl 2-diazo-3-(4hydroxyphenyl)propanoate (cf Tetrahedron Lett., 1971,4495) (8.58 g) in methanol (120 mL) was added over 10 minutes to a mixture of rhodium (II) acetate dimer (0.18 g) in methanol (50 mL) at room temperature under a nitrogen atmosphere. The resulting mixture was heated at reflux for 5 hrs, allowed to stand at room temperature for 15 hrs, then concentrated in vacuo. The residue was dissolved in ethyl acetate (500 mL), washed with water (3×300 mL) and brine (500 mL), dried (MgSO4) and evaporated. The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent to afford the title compound, mp 61-3° C. The resulting mixture was heated at reflux for 5 hrs concentrated in vacuo The residue was dissolved in ethyl acetate (500 mL) washed with water (3×300 mL) and brine (500 mL) dried (MgSO4) evaporated The resulting gum was chromatographed on silica gel with a gradient of 4% ethyl acetate to 6% ethyl acetate in dichloromethane as eluent

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

Procedure: 3-(4-Hydroxyphenyl)-2-methoxypropanoic acid methyl ester was alkylated with 2-(4-methanesulfonyloxyphenyl)ethylmethanesulfonate (described in Example 1a) using the same method as in Example 1 (b) to give 3-{4-[2-(4-methanesulfonyloxyphenyl)ethoxy]-phenyl}-2-methoxypropanoic acid methyl ester.