methyl 2-[(3R)-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetate

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

Procedure: 3-Chloromethyl-2-cyclopentylsulfanyl-pyridine (11 mg, 0.05 mmol) obtained in Step C of Preparation Example 8 and ((R)-6-hydroxy-2,3-dihydro-benzofuran-3-yl)-acetic acid methyl ester (10 mg, 0.05 mmol) obtained in Preparation Example 55 were used to react sequentially in the same manner as in Steps A and B of Example 1 to obtain the title compound (15 mg, 89%). obtained in Preparation Example 55 to react sequentially in the same manner as in Steps A and B of Example 1

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

Procedure: 3-Chloromethyl-2-cyclopentylsulfanyl-pyridine (11 mg, 0.05 mmol) obtained in Step C of Preparation Example 8 and ((R)-6-hydroxy-2,3-dihydro-benzofuran-3-yl)-acetic acid methyl ester (10 mg, 0.05 mmol) obtained in Preparation Example 55 were used to react sequentially in the same manner as in Steps A and B of Example 1 to obtain the title compound (15 mg, 89%). obtained in Preparation Example 55 to react sequentially in the same manner as in Steps A and B of Example 1

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [(3R)-6-Hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetic acid (R)-2-amino-1,1-diphenylpropan-1-ol salt (100 g) and sulfuric acid (30.26 g) were added to methanol (120 mL), and the mixture was stirred at 60° C. for 2 hr. After allowing to cool to room temperature, the solvent was concentrated under reduced pressure. To the residue were added toluene (831 mL), tetrahydrofuran (415 mL) and 1M hydrochloric acid (500 mL), and the mixture was partitioned. The organic layer was washed with water (500 mL), 5% aqueous sodium hydrogen carbonate solution (500 mL) and water (500 mL). The organic layer was concentrated, and toluene (110 mL) was added to the residue. The mixture was heated to 50° C., dissolved, allowed to cool to room temperature, and solid precipitation was confirmed. Normal heptane (220 mL) was added, and the mixture was stirred at room temperature for 5 hr. After cooling to 5° C., the solid was collected by filtration, washed with a mixed solution (1:2, 24 mL) of toluene-normal heptane. The solid was dried at 50° C. under reduced pressure to give the title compound (45.19 g). 99.6% ee. to cool to room temperature the solvent was concentrated under reduced pressure To the residue were added toluene (831 mL), tetrahydrofuran (415 mL) and 1M hydrochloric acid (500 mL) the mixture was partitioned The organic layer was washed with water (500 mL), 5% aqueous sodium hydrogen carbonate solution (500 mL) and water (500 mL) The organic layer was concentrated toluene (110 mL) was added to the residue The mixture was heated to 50° C. dissolved to cool to room temperature solid precipitation Normal heptane (220 mL) was added the mixture was stirred at room temperature for 5 hr After cooling to 5° C. the solid was collected by filtration washed with a mixed solution (1:2, 24 mL) of toluene-normal heptane The solid was dried at 50° C. under reduced pressure

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

Procedure: 3-Chloromethyl-2-cyclopentylsulfanyl-pyridine (11 mg, 0.05 mmol) obtained in Step C of Preparation Example 8 and ((R)-6-hydroxy-2,3-dihydro-benzofuran-3-yl)-acetic acid methyl ester (10 mg, 0.05 mmol) obtained in Preparation Example 55 were used to react sequentially in the same manner as in Steps A and B of Example 1 to obtain the title compound (15 mg, 89%). obtained in Preparation Example 55 to react sequentially in the same manner as in Steps A and B of Example 1