tert-Butyl acrylate → HCID 20825944, compound

Tri-tert-butylphosphine (3.0 g, 15.28 mmol) was added to a solution of tris(dibenzylideneacetone)dipalladium (4.2 g, 4.63 mmol) in 1,4-dioxane (45 ml), under argon, and the solution stirred for 30 minutes at room temperature. This solution was then added to a mixture of 6-benzyl-2-chloro-5,6,7,8-tetrahydro[1,6]naphthyridine (WO 9830560 Example 33b) (12 g, 46.3 mmol) and tert-butylacrylate (20.3 ml, 139 mmol) in triethylamine (45 ml), and the reaction was stirred under reflux for 17 hours. The cooled mixture was concentrated under reduced pressure and the residue partitioned between ethyl acetate (300 ml) and water (300 ml) and this mixture filtered through Arbocel®. The pH of the mixture was adjusted to 8 using sodium bicarbonate, the phases separated, and the aqueous layer re-extracted with ethyl acetate (2×100 ml). The combined organic solutions were dried over magnesium sulphate and evaporated under reduced pressure. The crude product was pre-adsorbed onto silica gel, and purified by column chromatography using an elution gradient of cyclohexane: ethyl acetate (84:16 to 66:34) to afford the title compound as an orange-red oil, (15.8 g).

1. stirringthe reaction was stirred
2. temperatureunder reflux for 17 hours
3. concentrationThe cooled mixture was concentrated under reduced pressure
4. customthe residue partitioned between ethyl acetate (300 ml) and water (300 ml)
5. filtrationthis mixture filtered through Arbocel®
6. customthe phases separated
7. extractionthe aqueous layer re-extracted with ethyl acetate (2×100 ml)
8. dry with materialThe combined organic solutions were dried over magnesium sulphate
9. customevaporated under reduced pressure
10. custompurified by column chromatography

ORD record

ord-00825116af92466d9be6ff5ebf27b32e

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06936619B2