Diisopropylamine → 5-[2-(2,4-Difluorophenyl)ethenyl]-2,2-dimethyl-3(2H)-furanone

To a solution of dry diisopropylamine (3.3 mL, 24 mM) in dry tetrahydrofuran (25 mL) at -78° C., was added dropwise 2.3N solution of n-butyllithium in hexane (10.4 mL,24mM). After the reaction solution was stirred 15 minutes, a solution of 2,2,5-trimethyl-3(2H)-furanone (2.0 g, 16 mm) in tetrahydrofuran (10 mL) was added dropwise. Hexamethylphosphoramide (4.4 mL, 24 mM) was then added dropwise after 30 minutes. Finally, 2,4-difluorobenzaldehyde (3.5 mL, 31.8 mM) in tetrahydrofuran (10 mL) was added in one portion. The reaction solution was stirred 10 minutes when trifluoroacetic anhydride (11.87 g, 55.7 mM) was added in one portion. Again, the reaction solution was stirred 15, minutes when triethylamine (5.6 g, 55.7 mM) was added and was allowed to warm to room temperature. The reaction solution was partitioned between saturated aqueous sodium chloride (50 mL) and diethyl ether (50 mL). The layers were separated. The organic layers were then washed with saturated aqueous sodium chloride (2×25 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give an orange liquid. The crude product was purified by chromatography (silica gel, pet. ether-ethyl acetate) to afford a yellow crystalline solid (2.6 g, 65% yield), m.p. 98.5°-100° C.

1. additionwas added in one portion
2. additionwas added
3. customThe reaction solution was partitioned between saturated aqueous sodium chloride (50 mL) and diethyl ether (50 mL)
4. customThe layers were separated
5. washThe organic layers were then washed with saturated aqueous sodium chloride (2×25 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto give an orange liquid
10. customThe crude product was purified by chromatography (silica gel, pet. ether-ethyl acetate)

ORDレコード

ord-d7b5719dccfd49bca7dbd25ecdbb694c

出典データセット

uspto-grants-1991_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05001126