P-Cymene → Ethyl 4,4,4-trifluoro-3-hydroxybutanoate

Temperature

35 °C

A solution of 50 mL of a mixture of formic acid-triethylamine (5:2 in molar ratio) and 70.1 mg of RuCl[(1R,2R)-p-TsNHCH(C6H5)CH(C6H5)NH2] (p-cymene) dissolved in 25 mL of tetrahydrofuran was stirred at 35° C., and a solution of 10.0 g of ethyl 4,4,4-trifluoro-3-oxobutanoate dissolved in 25 mL of tetrahydrofuran was added thereto over a period of 30 minutes. The reaction mixture was stirred at the same temperature for 21 hours and the conversion into the hydroxy compound was found to be 100%. After the reaction mixture was concentrated under reduced pressure using an evaporator, 20 mL of water and 40 mL of ethyl acetate were added to the resulting concentrate and then a saturated sodium carbonate aqueous solution was added thereto under stirring until the pH became 7 or higher. After the separation of the ethyl acetate layer, the water layer was further extracted with 25 mL of ethyl acetate. Then, the ethyl acetate layer was combined with the previous ethyl acetate layer and the combined layer was concentrated. The resulting concentrate was distilled under reduced pressure (88-89° C./2660 Pa) to obtain 8.96 g of optically active ethyl 4,4,4-trifluoro-3-hydroxybutanoate (yield 88.6%). Upon the measurement under the above conditions, the optical purity of the resulting optically active ethyl 4,4,4-trifluoro-3-hydroxybutanoate was found to be 94.2% e.e.

1. additionwas added
2. stirringThe reaction mixture was stirred at the same temperature for 21 hours
3. concentrationAfter the reaction mixture was concentrated under reduced pressure
4. customan evaporator, 20 mL of water and 40 mL of ethyl acetate
5. additionwere added to the resulting
6. concentrationconcentrate
7. additiona saturated sodium carbonate aqueous solution was added
8. stirringunder stirring until the pH
9. customAfter the separation of the ethyl acetate layer
10. extractionthe water layer was further extracted with 25 mL of ethyl acetate
11. concentrationthe combined layer was concentrated
12. concentrationThe resulting concentrate
13. distillationwas distilled under reduced pressure (88-89° C./2660 Pa)

ORD record

ord-3b83dfbdb46f4025a47af23cc343ddba

Source dataset

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06723871B2