METHYL (R)-2-HYDROXY-3-PHENYLPROPIONATE

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

Procedure: Following the procedure of Cohen (J. Am. Chem. Soc., 1964, 86, 5326), the resultant compound from Example 89 (8.6 g, 52 mmol) was dissolved in dry methanol (250 ml). p-Toluenesulfonic acid (2 g, 10.5 mmol) was added and the solution was refluxed for 2 h. The cooled solution was concentrated in vacuo and the residue was dissolved in ether (400 ml). The ether solution was washed with saturated aqueous NaHCO3 (3×50 ml), water (2×50 ml), 0.1N H2SO4 (1×50 ml), water (1×50 ml), dried over Na2SO4, and concentrated in vacuo to afford a colorless solid. The solid was recrystallized from hexane to provide the title compound as colorless needles (7.7 g, 83%); mp=46°-47° C. the solution was refluxed for 2 h The cooled solution was concentrated in vacuo the residue was dissolved in ether (400 ml) The ether solution was washed with saturated aqueous NaHCO3 (3×50 ml), water (2×50 ml), 0.1N H2SO4 (1×50 ml), water (1×50 ml) dried over Na2SO4 concentrated in vacuo to afford a colorless solid The solid was recrystallized from hexane

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

Procedure: The title compound was prepared from 4′-(2-benzyl-benzofuran-3-yl)-3,5-dibromo-biphenyl-4-ol, and (R)-(+)-3-phenyllactic acid methyl ester, in substantially the same manner, as described in Example 1, steps g-h, and was obtained as a white solid, mp 90-92° C.; MS m/e 679 (M−H+; was obtained as a white solid, mp 90-92° C.

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

Procedure: The title compound was prepared from 4′-(2-benzyl-benzofuran-3-yl)-3,5-dibromo-biphenyl-4-ol, and (R)-(+)-3-phenyllactic acid methyl ester, in substantially the same manner, as described in Example 1, steps g-h, and was obtained as a white solid, mp 90-92° C.; MS m/e 679 (M−H+; was obtained as a white solid, mp 90-92° C.

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

Procedure: Following the procedure of Cohen (J. Am. Chem. Soc., 1964, 86, 5326), the resultant compound from Example 89 (8.6 g, 52 mmol) was dissolved in dry methanol (250 ml). p-Toluenesulfonic acid (2 g, 10.5 mmol) was added and the solution was refluxed for 2 h. The cooled solution was concentrated in vacuo and the residue was dissolved in ether (400 ml). The ether solution was washed with saturated aqueous NaHCO3 (3×50 ml), water (2×50 ml), 0.1N H2SO4 (1×50 ml), water (1×50 ml), dried over Na2SO4, and concentrated in vacuo to afford a colorless solid. The solid was recrystallized from hexane to provide the title compound as colorless needles (7.7 g, 83%); mp=46°-47° C. the solution was refluxed for 2 h The cooled solution was concentrated in vacuo the residue was dissolved in ether (400 ml) The ether solution was washed with saturated aqueous NaHCO3 (3×50 ml), water (2×50 ml), 0.1N H2SO4 (1×50 ml), water (1×50 ml) dried over Na2SO4 concentrated in vacuo to afford a colorless solid The solid was recrystallized from hexane

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

Procedure: To a solution of (R)-2-hydroxy-3-phenylpropionic acid methyl ester from Step A (1.62 g, 10.9 mol) and triethylamine (3.0 mL, 21.8 mol) in dichloromethane (21.8 mL) at 0° C. was added dropwise methanesulfonyl chloride (1.28 mL, 16.4 mol). The reaction mixture was stirred at 0° C. for 1 h and was diluted with diethyl ether (200 mL) and washed with saturated ammonium chloride solution and brine. The organic layer was separated, dried with magnesium sulfate, filtered and concentrated in vacuo to give a light yellow solid 2.43 g (73%), which was used without further purification. washed with saturated ammonium chloride solution and brine The organic layer was separated dried with magnesium sulfate filtered concentrated in vacuo

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

Procedure: To a solution of (R)-2-hydroxy-3-phenylpropionic acid (1.5 g, 12.9 mol) in methanol (18 mL) at 0° C. was added concentrated sulfuric acid (0.2 mL). The reaction mixture was stirred at 0° C. for 30 min and warmed to room temperature for 24 h. Concentration in vacuo gave a residue which was diluted with diethyl ether (200 mL) and washed with water, saturated sodium bicarbonate and brine. The organic layer was separated, dried with sodium sulfate, filtered and concentrated in vacuo giving a white solid 1.62 g (85%), which was used without further purification. warmed to room temperature for 24 h Concentration in vacuo gave a residue which washed with water, saturated sodium bicarbonate and brine The organic layer was separated dried with sodium sulfate filtered concentrated in vacuo

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

Procedure: To a solution of (R)-2-hydroxy-3-phenylpropionic acid methyl ester from Step A (1.62 g, 10.9 mol) and triethylamine (3.0 mL, 21.8 mol) in dichloromethane (21.8 mL) at 0° C. was added dropwise methanesulfonyl chloride (1.28 mL, 16.4 mol). The reaction mixture was stirred at 0° C. for 1 h and was diluted with diethyl ether (200 mL) and washed with saturated ammonium chloride solution and brine. The organic layer was separated, dried with magnesium sulfate, filtered and concentrated in vacuo to give a light yellow solid 2.43 g (73%), which was used without further purification. washed with saturated ammonium chloride solution and brine The organic layer was separated dried with magnesium sulfate filtered concentrated in vacuo

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

Procedure: To a solution of (R)-2-hydroxy-3-phenylpropionic acid (1.5 g, 12.9 mol) in methanol (18 mL) at 0° C. was added concentrated sulfuric acid (0.2 mL). The reaction mixture was stirred at 0° C. for 30 min and warmed to room temperature for 24 h. Concentration in vacuo gave a residue which was diluted with diethyl ether (200 mL) and washed with water, saturated sodium bicarbonate and brine. The organic layer was separated, dried with sodium sulfate, filtered and concentrated in vacuo giving a white solid 1.62 g (85%), which was used without further purification. warmed to room temperature for 24 h Concentration in vacuo gave a residue which washed with water, saturated sodium bicarbonate and brine The organic layer was separated dried with sodium sulfate filtered concentrated in vacuo

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

Procedure: The title compound was prepared from 4′-(2-benzyl-benzofuran-3-yl)-3,5-dibromo-biphenyl-4-ol, and (R)-(+)-3-phenyllactic acid methyl ester, in substantially the same manner, as described in Example 1, steps g-h, and was obtained as a white solid, mp 90-92° C.; MS m/e 679 (M−H+; was obtained as a white solid, mp 90-92° C.

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

Procedure: Prepared from 11-(3, 5-dibromo-4-hydroxy-phenyl)-benzo[b]naphtho[2,3-d ]thiophene-6-carbonitrile (Example 58) and (R)-2-hydroxy-3-phenylpropionic acid, methyl ester (Example 97). White solid: mp 176-178° C.: NMR (CDCl3); δ8.36 (ddd, J =8,1,1 Hz, 1 H), 7.85 (d, J=8 Hz, 1 H), 7.77 (ddd, J=8, 8, 2 Hz, 1 H), 7.58 (d, J=2 Hz, 1 H), 7.61-7.54 (m, 2 H), 7.56 (d, J=2 Hz, 1 H), 7.47 (ddd, J=8, 8, 1 Hz, 1 H), 7.41 (ddd, J=8, 1, 1, 2 H ), 7.36-7.26 (m, 3 H), 7.20 (ddd, J=8, 8, 1, 1 H), 6.75 (ddd, J =8, 1, 1 Hz, 1 H), 5.46 (t, J=7 Hz, 1 H), 3.59 (d, J=7 Hz, 2 H); MS (-FAB): [M-H]-, 2 bromine isotope pattern, 654 (2%), 656 (4%) 658 (2%); Anal. Calc. for C32H19Br2NO3S: C, 58.47, H, 2.91, N, 2.13 Found: C, 58.23, H, 2.69, N, 2.03.

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

Procedure: To a solution of (R)-2-hydroxy-3-phenylpropionic acid methyl ester from Step A (1.62 g, 10.9 mol) and triethylamine (3.0 mL, 21.8 mol) in dichloromethane (21.8 mL) at 0° C. was added dropwise methanesulfonyl chloride (1.28 mL, 16.4 mol). The reaction mixture was stirred at 0° C. for 1 h and was diluted with diethyl ether (200 mL) and washed with saturated ammonium chloride solution and brine. The organic layer was separated, dried with magnesium sulfate, filtered and concentrated in vacuo to give a light yellow solid 2.43 g (73%), which was used without further purification. washed with saturated ammonium chloride solution and brine The organic layer was separated dried with magnesium sulfate filtered concentrated in vacuo

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

Procedure: To a solution of (R)-2-hydroxy-3-phenylpropionic acid (1.5 g, 12.9 mol) in methanol (18 mL) at 0° C. was added concentrated sulfuric acid (0.2 mL). The reaction mixture was stirred at 0° C. for 30 min and warmed to room temperature for 24 h. Concentration in vacuo gave a residue which was diluted with diethyl ether (200 mL) and washed with water, saturated sodium bicarbonate and brine. The organic layer was separated, dried with sodium sulfate, filtered and concentrated in vacuo giving a white solid 1.62 g (85%), which was used without further purification. warmed to room temperature for 24 h Concentration in vacuo gave a residue which washed with water, saturated sodium bicarbonate and brine The organic layer was separated dried with sodium sulfate filtered concentrated in vacuo