Acetic Acid → Ethyl 9-oxo-3-thiabicyclo[3.3.1]nonane-7-carboxylate

A mixture of triethylamine (10.1 ml, 72 mmol) and 3,6-dihydro-4-(1-pyrrolidinyl)-2H-thiopyran (12.9 g, 76 mmol, prepared according to a procedure described in Tetrahedron Asymmetry 1997, 1811-1820) in anhydrous acetonitrile (55 ml) was heated to reflux, then ethyl 3-bromo-2-(bromomethyl)propionate (14.6 g, 53 mmol) in dry acetonitrile (42 ml) was added dropwise over a period of 45 min. The resulting reaction mixture was refluxed for another 1.5 hours, then cooled to room temperature before a 10% aqueous acetic acid solution (5.2 ml) was added. The mixture was then refluxed for 1 hour and evaporated to dryness. Brine was added to the residue, the aqueous phase was extracted with ethyl acetate, the combined organic extracts were dried over anhydrous sodium sulphate, filtered and concentrated in vacuo to yield 9-oxo-3-thia-bicyclo[3.3.1]nonane-7-carboxylic acid ethyl ester as a brown oil (15.5 g).

1. customprepared
2. temperaturewas heated
3. temperatureto reflux
4. customThe resulting reaction mixture
5. temperaturewas refluxed for another 1.5 hours
6. additionwas added
7. temperatureThe mixture was then refluxed for 1 hour
8. customevaporated to dryness
9. additionBrine was added to the residue
10. extractionthe aqueous phase was extracted with ethyl acetate
11. dry with materialthe combined organic extracts were dried over anhydrous sodium sulphate
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD record

ord-e235a0f75ca946ec9ac635207cbb5fa0

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08524737B2