4-Nitrobenzoic Acid → 1(S)-[2(S)-(2,5-Difluoro-phenyl)oxiranyl]-ethanol

Temperatur

0 °C

DEAD (870 mg; 2 mmol) and p-nitrobenzoic acid (337 mg; 2 mmol) were dissolved in dry THF (3 ml) and the solution was cooled to 0° C. Then 1(R)-[2(S)-(2,5-Difluoro-phenyl)-oxiranyl]-ethanol (100 mg; 0.5 mmol) and triphenylphosphine (524 mg; 2 mmol) is dissolved in dry THF (10 ml) were added dropwise at such a rate to maintain the temperature below 10° C. The mixture was then allowed to react to completion at 20° C. for 20 hours. Half of the solvent was removed under reduced pressure. The reaction mixture is diluted with diethyl ether (80 ml) and washed with an aqueous saturated ammonium chloride solution. The organic phase is dried over magnesium sulfate. The solids are filtered off and the solvent is removed under reduced pressure. The residue is dissolved in methanol (25 ml) and treated with potassium carbonate (450 mg). The reaction mixture is diluted with an aqueous saturated ammonium chloride solution (30 ml). The reaction mixture is extracted with ethyl acetate (2 times 20 ml). The combined organic phases are washed with water (2 times 30 ml) and with brine (2 times 30 ml). The organic phase is dried over magnesium sulfate. The solids are filtered off and the solvent is removed under reduced pressure. The crude residue is purified by chromatography (Petrole ether/ethyl acetate 20:1). 53 mg (yield: 53%) of desired 1(S)-[2(S)-(2,5-Difluoro-phenyl)-oxiranyl]-ethanol was obtained as a colorless oil. The HPLC purity is 76%.

1. additionwere added dropwise at such a rate
2. temperatureto maintain the temperature below 10° C
3. customto react to completion at 20° C. for 20 hours
4. customHalf of the solvent was removed under reduced pressure
5. additionThe reaction mixture is diluted with diethyl ether (80 ml)
6. washwashed with an aqueous saturated ammonium chloride solution
7. dry with materialThe organic phase is dried over magnesium sulfate
8. filtrationThe solids are filtered off
9. customthe solvent is removed under reduced pressure
10. dissolutionThe residue is dissolved in methanol (25 ml)
11. additiontreated with potassium carbonate (450 mg)
12. additionThe reaction mixture is diluted with an aqueous saturated ammonium chloride solution (30 ml)
13. extractionThe reaction mixture is extracted with ethyl acetate (2 times 20 ml)
14. washThe combined organic phases are washed with water (2 times 30 ml) and with brine (2 times 30 ml)
15. dry with materialThe organic phase is dried over magnesium sulfate
16. filtrationThe solids are filtered off
17. customthe solvent is removed under reduced pressure
18. customThe crude residue is purified by chromatography (Petrole ether/ethyl acetate 20:1)

ORD-Eintrag

ord-8f49ad57d79541b2a63e5244ccbbb162

Quelldatensatz

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08076494B2