(2R)-2-Hexyloxirane → (alphaS,gammaR)-alpha-(4-butylphenyl)-gamma-hexyl-gamma-butyrolactone

Temperature

-60 °C

4-Butylphenylacetic acid (5 g) was dissolved in THF (100 ml), followed by cooling the solution down to -60° C., dropwise adding a tetrahydrofuran solution of LDA (10.4 mmol) over 30 minutes, raising the temperature up to 0° C., agitating for 30 minutes, cooling down to -60° C., dropwise adding a mixed solution of (R)-1,2-epoxyoctane (3.4 g) with anhydrous THF (5 ml) over 10 minutes, gradually raising the temperature, agitating at room temperature overnight, pouring the reaction solution in ice water (100 ml) and toluene (200 ml), washing the resulting organic layer with 6N--HCl, 2N--NaOH and saturated NaCl aqueous solution in this order, drying over anhydrous magnesium sulfate, concentrating the organic layer under reduced pressure, placing the resulting concentrate in a 1 l three-necked flask, adding toluene (250 ml) and p-toluenesulfonic acid (1.1 g), heating the mixture under reflux for 4 hours, dehydrating with a Dien-Stark type drain tube, adding ice water (100 ml), washing the organic layer with 6N--HCl, 2N--NaOH and saturated NaCl aqueous solution in this order, drying over magnesium sulfate, concentrating the organic layer under reduced pressure, separation-purifying according to chromatography and recrystallizing from ethanol to obtain (αS,γR)-α-(4-butylphenyl)-γ-hexyl-γ-butyrolactone (trans-form) (0.8 g). m.p.: 37.7° C.

1. temperatureraising the temperature up to 0° C.
2. temperaturecooling down to -60° C.
3. temperaturegradually raising the temperature
4. stirringagitating at room temperature overnight
5. washtoluene (200 ml), washing the resulting organic layer with 6N
6. dry with materialHCl, 2N--NaOH and saturated NaCl aqueous solution in this order, drying over anhydrous magnesium sulfate
7. concentrationconcentrating the organic layer under reduced pressure
8. concentrationconcentrate in a 1 l three-necked flask
9. additionadding toluene (250 ml) and p-toluenesulfonic acid (1.1 g)
10. temperatureheating the mixture
11. temperatureunder reflux for 4 hours
12. additionadding ice water (100 ml)
13. washwashing the organic layer with 6N
14. dry with materialHCl, 2N--NaOH and saturated NaCl aqueous solution in this order, drying over magnesium sulfate
15. concentrationconcentrating the organic layer under reduced pressure
16. customseparation-purifying
17. customrecrystallizing from ethanol

ORD record

ord-080c1ed82b8441a19a14ee6e5a2d0574

Source dataset

uspto-grants-1993_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05256330