Tetrahydrofuran → (2E)-3-[(2S)-2-methyltetrahydro-2H-pyran-4-yl]acrylic acid

Temperature

-10 °C

To a suspension of (methoxymethyl)triphenyl phosphine chloride (32 g) in anhydrous THF (160 ml), cooled to −10° C., was added dropwise sodium bis(trimethylsilyl) amide (46.7 ml of 2M solution in THF). The reaction mixture was stirred for 1 hour and then a solution of (2S)-2-methyltetrahydro-4H-pyran-4-one (7.1 g) in anhydrous THF (20 ml) was added over 5 minutes. The resulting mixture was allowed to warm to room temperature and stirred for 3 hours. The reaction was quenched with water (50 ml) and extracted with diethyl ether (3×100 ml). The organics were dried and evaporated to dryness. The resulting gum was treated with diethyl ether and filtered. The organics were evaporated to dryness and the resulting residue was purified by chromatography on silica eluting with ethyl acetate/isohexane (1:9) to give the title compound (˜1:1 E/Z mixture of isomers) as an oil. Yield 6.22 g. NMR CDCl3 1.1 (dd, 3H), 1.45-2.1 (m, 3H), 2.4-2.55 (m, 1H), 3.2 (m, 2H), 3.4 (s, 3H), 3.85 (m, 1H) 5.7 (m, 1H).

1. temperatureto warm to room temperature
2. stirringstirred for 3 hours
3. customThe reaction was quenched with water (50 ml)
4. extractionextracted with diethyl ether (3×100 ml)
5. customThe organics were dried
6. customevaporated to dryness
7. additionThe resulting gum was treated with diethyl ether
8. filtrationfiltered
9. customThe organics were evaporated to dryness
10. customthe resulting residue was purified by chromatography on silica eluting with ethyl acetate/isohexane (1:9)

ORD record

ord-82a97b9b1fbb4b45b16040c6cdcb9bde

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07615555B2