(2S,3R)-2-aminobutane-1,3-diol

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

Procedure: 5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy]phenyl}-1H-pyrrole-2-carboxylic acid (1.63 g, 3.64 mmol) synthesized in Example (106c) was dissolved in methanol (20 mL), and D-allo-threoninol (1.05 g, 9.99 mmol) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride n hydrate (2.00 g, 7.23 mmol) were added, followed by stirring at room temperature for 1 day under nitrogen atmosphere. After the solvent was distilled off under reduced pressure, a saturated aqueous ammonium chloride solution (50 mL) was added, and extraction was carried out with methylene chloride (80 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The resulting residue was purified using silica gel column chromatography (elution solvent: methanol/methylene chloride=3%-7%) to afford the desired compound (1.70 g, yield 87%) as a white foam. After the solvent was distilled off under reduced pressure a saturated aqueous ammonium chloride solution (50 mL) was added extraction The organic layer was washed with saturated brine subsequently dried over anhydrous magnesium sulfate The resulting residue was purified silica gel column chromatography (elution solvent: methanol/methylene chloride=3%-7%)

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

Procedure: 5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxylic acid (1.47 g, 3.29 mmol) synthesized in Example (78k), commercially available D-allo-threoninol (0.52 g, 4.94 mmol), HOBT•H2O (0.49 g, 3.62 mmol) and N-methylmorpholine (0.72 mL, 6.58 mmol) were dissolved in N,N-dimethylformamide (10 mL), and WSCI•HCl (0.76 g, 3.95 mmol) was added at room temperature, followed by stirring for 5.5 hours under nitrogen atmosphere. To the reaction solution, saturated brine (40 mL) was added, and extraction was carried out with ethyl acetate (70 mL). After washed with saturated brine, drying was carried out over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: methanol/methylene chloride=0%-6%) to afford the desired compound (1.42 g, 81%) as a white solid. extraction After washed with saturated brine drying The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: methanol/methylene chloride=0%-6%)

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

Procedure: 5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxylic acid (1.47 g, 3.29 mmol) synthesized in Example (78k), commercially available D-allo-threoninol (0.52 g, 4.94 mmol), HOBT.H2O (0.49 g, 3.62 mmol) and N-methylmorpholine (0.72 mL, 6.58 mmol) were dissolved in N,N-dimethylformamide (10 mL), and WSCI.HCl (0.76 g, 3.95 mmol) was added at room temperature, followed by stirring for 5.5 hours under nitrogen atmosphere. To the reaction solution, saturated brine (40 mL) was added, and extraction was carried out with ethyl acetate (70 mL). After washed with saturated brine, drying was carried out over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: methanol/methylene chloride=0%-6%) to afford the desired compound (1.42 g, 81%) as a white solid. extraction After washed with saturated brine drying The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: methanol/methylene chloride=0%-6%)

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

Procedure: 5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy]phenyl}-1H-pyrrole-2-carboxylic acid (1.63 g, 3.64 mmol) synthesized in Example (106c) was dissolved in methanol (20 mL), and D-allo-threoninol (1.05 g, 9.99 mmol) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride n hydrate (2.00 g, 7.23 mmol) were added, followed by stirring at room temperature for 1 day under nitrogen atmosphere. After the solvent was distilled off under reduced pressure, a saturated aqueous ammonium chloride solution (50 mL) was added, and extraction was carried out with methylene chloride (80 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The resulting residue was purified using silica gel column chromatography (elution solvent: methanol/methylene chloride=3%-7%) to afford the desired compound (1.70 g, yield 87%) as a white foam. After the solvent was distilled off under reduced pressure a saturated aqueous ammonium chloride solution (50 mL) was added extraction The organic layer was washed with saturated brine subsequently dried over anhydrous magnesium sulfate The resulting residue was purified silica gel column chromatography (elution solvent: methanol/methylene chloride=3%-7%)

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

Procedure: 5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxylic acid (1.47 g, 3.29 mmol) synthesized in Example (78k), commercially available D-allo-threoninol (0.52 g, 4.94 mmol), HOBT•H2O (0.49 g, 3.62 mmol) and N-methylmorpholine (0.72 mL, 6.58 mmol) were dissolved in N,N-dimethylformamide (10 mL), and WSCI•HCl (0.76 g, 3.95 mmol) was added at room temperature, followed by stirring for 5.5 hours under nitrogen atmosphere. To the reaction solution, saturated brine (40 mL) was added, and extraction was carried out with ethyl acetate (70 mL). After washed with saturated brine, drying was carried out over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: methanol/methylene chloride=0%-6%) to afford the desired compound (1.42 g, 81%) as a white solid. extraction After washed with saturated brine drying The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: methanol/methylene chloride=0%-6%)