ETHYL-3-HYDROXY-3-PHENYL PROPIONATE

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Under nitrogen atmosphere, 30 mL of THF was added to 3.96 g (6.50 mmol, 0.65 equivalent (equivalent relative to a carbonyl compound as a starting raw material; the same, hereinafter)) of (BrZnCH2COOEt.THF)2. Under argon atmosphere, a solution of 1.06 g (10 mmol) of benzaldehyde in 5 mL of THF was added dropwise while stirring at 0˜5° C. The mixture was stirred at 0˜5° C. for 3 hours. 25 mL of 1N hydrochloric acid was added dropwise at 20° C. or lower, followed by dilution with 50 mL of ethyl acetate. Then, the layers were separated. The organic layer was washed successively with 10 mL (×2) of 1N hydrochloric acid, 20 mL of an aqueous saturated sodium chloride solution, 20 mL (×2) of an aqueous saturated sodium bicarbonate solution and 20 mL of an aqueous saturated sodium chloride solution. After washing, the organic layer was dried with anhydrous magnesium sulfate. Concentration under reduced pressure afforded 1.76 g of the desired product (yield 91%). The mixture was stirred at 0˜5° C. for 3 hours Then, the layers were separated The organic layer was washed successively with 10 mL (×2) of 1N hydrochloric acid, 20 mL of an aqueous saturated sodium chloride solution, 20 mL (×2) of an aqueous saturated sodium bicarbonate solution and 20 mL of an aqueous saturated sodium chloride solution After washing the organic layer was dried with anhydrous magnesium sulfate Concentration under reduced pressure

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

Procedure: Ethyl benzoylacetate (1) (19.21 g; 0.10 mol) was dissolved in 95% ethanol (100 mL) in a pressure bottle. The bottle was purged with nitrogen and 5% palladium on carbon (960 mg; 5 weight %) was added. The vessel was placed under 45 psi H2 and shaken on a Parr apparatus for 14 hours, at which time H2 uptake had halted and thin layer chromatographic analysis indicated (1) was present. The reaction mixture was suction-filtered through Celite with a top sand layer (to prevent channels) and eluted with ether to remove the catalyst. The filtrate was concentrated to afford (2), racemic ethyl 3-phenyl-3-hydroxypropionate (19.17 g; 99%) which was pure by tlc and 1H nmr analysis. 1H nmr (300 MHz, CDCl3): 7.4-7.2 (5H, m); 5.130(1H,dd,J=4.36, 8.48 Hz); 4.178 (2H, q, J=7.17 Hz); 3.2(1H, br s); 2 764(1H, dd, J=8.58, 16.30 Hz); 2.691 (1H, dd, J=4.33, 16.33 Hz); 1.259(3H, t, J=7.17 Hz). IR (neat film, cm-1) 3450 (s,b); 1720(s); 1605(w). EIMS (m/e): 194 (M+); 165 (2%, M+ - Et); 149 (5%, M+ -EtO). The bottle was purged with nitrogen and 5% palladium on carbon (960 mg; 5 weight %) was added The reaction mixture was suction-filtered through Celite with a top sand layer (to prevent channels) eluted with ether to remove the catalyst The filtrate was concentrated

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

Procedure: The mixture of 5.0 g (25.7 mmol) of ethyl 3-phenyl-3-hydroxypropionate, 1.83 g (13 mmol) of vinyl caproate and 1.0 g of lipase PS was stirred at room temperature for 35 hours. After the lipase was removed by filtration, the filtrate was eluted by column chromatography (eluting solution; 9/1 of toluene/ethyl acetate) to obtain 2.2 g (>99%ee) of (-)-ethyl 3-phenyl-3-hydroxypropionate and 4.1 g (about 90%ee) of (+)-ethyl 3-phenyl-3-hexanoyloxypropionate. After the lipase was removed by filtration the filtrate was eluted by column chromatography (eluting solution; 9/1 of toluene/ethyl acetate)

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

Procedure: Under nitrogen atmosphere, 30 mL of THF was added to 3.96 g (6.50 mmol, 0.65 equivalent (equivalent relative to a carbonyl compound as a starting raw material; the same, hereinafter)) of (BrZnCH2COOEt.THF)2. Under argon atmosphere, a solution of 1.06 g (10 mmol) of benzaldehyde in 5 mL of THF was added dropwise while stirring at 0˜5° C. The mixture was stirred at 0˜5° C. for 3 hours. 25 mL of 1N hydrochloric acid was added dropwise at 20° C. or lower, followed by dilution with 50 mL of ethyl acetate. Then, the layers were separated. The organic layer was washed successively with 10 mL (×2) of 1N hydrochloric acid, 20 mL of an aqueous saturated sodium chloride solution, 20 mL (×2) of an aqueous saturated sodium bicarbonate solution and 20 mL of an aqueous saturated sodium chloride solution. After washing, the organic layer was dried with anhydrous magnesium sulfate. Concentration under reduced pressure afforded 1.76 g of the desired product (yield 91%). The mixture was stirred at 0˜5° C. for 3 hours Then, the layers were separated The organic layer was washed successively with 10 mL (×2) of 1N hydrochloric acid, 20 mL of an aqueous saturated sodium chloride solution, 20 mL (×2) of an aqueous saturated sodium bicarbonate solution and 20 mL of an aqueous saturated sodium chloride solution After washing the organic layer was dried with anhydrous magnesium sulfate Concentration under reduced pressure

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

Procedure: Ethyl 3-hydroxy-3-phenylpropanoate (19 g, 0.1 mole) was refluxed in a solution of KOH (10 g, 0.2 mole) in ethanol for two hours. The solvent was removed in vacuo and the residue was dissolved in H2O. The H2O solution was extracted with ethyl ether, then acidified with 37% hydrochloric acid. The oily product was extracted out with chloroform and the chloroform was removed in vacuo to yield 10 g (62.5%). The solvent was removed in vacuo the residue was dissolved in H2O The H2O solution was extracted with ethyl ether The oily product was extracted out with chloroform the chloroform was removed in vacuo to yield 10 g (62.5%)