Ethyl (E)-3-[6-(4-toluoyl)-2-pyridyl]acrylate → Triprolidine

A solution of 25 mL of 1.6 M n-BuLi/hexanes was added to a stirred and cooled (0° C.) suspension of (2-pyrrolidinoethyl)triphenylphosphonium bromide (17.24 g, 39.18 mmol) in dry THF (250 mL) over a period of ˜4 min. The ylide-forming reaction mixture was stirred an additional 10 min at 0° C., followed by the addition of one aliquot of a solution of 5c (4.52 g, 15.3 mmol) in dry THF (75 mL). After stirring at 0° C. for only 2 min, the reaction mixture was quenched by the addition of water (100 mL). The reaction mixture was then extracted twice with EtOAc and the combined organics were dried with Na2SO4, filtered, and evaporated to dryness. Chromatography over silica gel using MeOH/EtOAc (starting at 5% MeOH) gave 1.42 g (25%) of E,E-7c as a yellow crystalline solid and 2.42 g (42%) of E,E-7c. The structure of the products were confirmed by 1H NMR and MS. (Triprolidine ester E,E-7e was similarly prepared.)

1. temperaturecooled
2. customThe ylide-forming reaction mixture
3. stirringwas stirred an additional 10 min at 0° C.
4. stirringAfter stirring at 0° C. for only 2 min
5. customthe reaction mixture was quenched by the addition of water (100 mL)
6. extractionThe reaction mixture was then extracted twice with EtOAc
7. dry with materialthe combined organics were dried with Na2SO4
8. filtrationfiltered
9. customevaporated to dryness
10. customgave 1.42 g (25%) of E,E-7c as a yellow crystalline solid and 2.42 g (42%) of E,E-7c

ORD record

ord-1bbd29704f6a488ab98da9341daf764d

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07317026B2