calcium;ethanolate

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of calcium ethoxide (816 mg, 6.3 mmol), butene oxide (5.2 mL, 93 mmol) and 2,4-diiodophenol (2.17 g, 6.3 mmol) is heated in a sealed flask at 80° C. for 18 h. The reaction mixture is allowed to cool, poured into 1N HCl and extracted three times with CH2Cl2. The combined organic extracts are dried (Na2SO4), filtered and concentrated in vacuo. The resulting material is purified by column chromatography (two columns, step gradient of 30-40-50% CH2Cl2 in hexanes) to give 1-(2,4-diiodophenoxy)butan-2-ol as a clear oil (1.73 g, 67%).1H NMR (400 MHz, CDCl3) δ 8.04, 7.56, 6.57, 4.03, 3.9, 3.84, 2.42, 1.65, 1.04. to cool extracted three times with CH2Cl2 The combined organic extracts are dried (Na2SO4) filtered concentrated in vacuo The resulting material is purified by column chromatography (two columns, step gradient of 30-40-50% CH2Cl2 in hexanes)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of calcium ethoxide (816 mg, 6.3 mmol), butene oxide (5.2 mL, 93 mmol) and 2,4-diiodophenol (2.17 g, 6.3 mmol) is heated in a sealed flask at 80° C. for 18 h. The reaction mixture is allowed to cool, poured into 1N HCl and extracted three times with CH2Cl2. The combined organic extracts are dried (Na2SO4), filtered and concentrated in vacuo. The resulting material is purified by column chromatography (two columns, step gradient of 30-40-50% CH2Cl2 in hexanes) to give 1-(2,4-diiodophenoxy)butan-2-ol as a clear oil (1.73 g, 67%).1H NMR (400 MHz, CDCl3) δ 8.04, 7.56, 6.57, 4.03, 3.9, 3.84, 2.42, 1.65, 1.04. to cool extracted three times with CH2Cl2 The combined organic extracts are dried (Na2SO4) filtered concentrated in vacuo The resulting material is purified by column chromatography (two columns, step gradient of 30-40-50% CH2Cl2 in hexanes)

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

Procedure: 4.6 g of calcium diethoxide was dissolved in 500 mL of methanol, to which a methanol (300 mL) solution of 30.8 g of (2S)-3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl]-2-isopropoxypropionic acid was then added, followed by stirring the reaction mixture overnight at room temperature. Insoluble matter in the reaction mixture was filtered, and the solvent was distilled off under a reduced pressure. To the residue were added 250 mL of methanol and 60 mL of water, followed by heating the reaction mixture to reflux. The reaction mixture was then cooled, followed by filtering the precipitated solid to obtain 32 g of the title compound as a crude product. To this compound was added 1.5 L of ethanol, and the reaction mixture was heated to reflux. Insoluble matter was hot-filtered, and the solution was again heated to reflux. To the reaction mixture was added 20 ml of water to slowly cool the mixture, and the reaction mixture was stirred overnight at room temperature. The precipitated solid was filtered, washed with ethanol:water=9:1, and subjected to forced-air drying at 40° C. for 18 hours. There was obtained 29 g of the title compound in the form of white crystal. The 1H-NMR data thereof coincided with that of the compound of Example 1-(15). was then added Insoluble matter in the reaction mixture was filtered the solvent was distilled off under a reduced pressure To the residue were added 250 mL of methanol and 60 mL of water by heating the reaction mixture to reflux The reaction mixture was then cooled by filtering the precipitated solid

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of calcium ethoxide (816 mg, 6.3 mmol), butene oxide (5.2 mL, 93 mmol) and 2,4-diiodophenol (2.17 g, 6.3 mmol) is heated in a sealed flask at 80° C. for 18 h. The reaction mixture is allowed to cool, poured into 1N HCl and extracted three times with CH2Cl2. The combined organic extracts are dried (Na2SO4), filtered and concentrated in vacuo. The resulting material is purified by column chromatography (two columns, step gradient of 30-40-50% CH2Cl2 in hexanes) to give 1-(2,4-diiodophenoxy)butan-2-ol as a clear oil (1.73 g, 67%).1H NMR (400 MHz, CDCl3) δ 8.04, 7.56, 6.57, 4.03, 3.9, 3.84, 2.42, 1.65, 1.04. to cool extracted three times with CH2Cl2 The combined organic extracts are dried (Na2SO4) filtered concentrated in vacuo The resulting material is purified by column chromatography (two columns, step gradient of 30-40-50% CH2Cl2 in hexanes)