Cyclobutanone → 6-Chlorospiro[chroman-2,1'-cyclobutan]-4-one

To a stirred solution of 5′-chloro-2′-hydroxy acetophenone (5.0 g, 29.308 mmol) in methanol (50 ml) was added pyrrolidine (4.16 g, 58.616 mmol) followed by cyclobutanone (4.1 g, 58.616 mmol) at room temperature. The reaction mixture was heated to reflux under nitrogen for 14 h. The solvent was evaporated under reduced pressure and the residue obtained was diluted with water (100 ml) and the mixture was acidified to pH 4.0. The mixture was extracted with chloroform (3×100 ml). The combined organic extracts were washed with water (100 ml), brine (50 ml) and dried over anhydrous sodium sulfate. The residue obtained after evaporation of the solvent was purified by silica gel column chromatography using 15% ethyl acetate in petroleum ether to give 6.3 g of the product as a white solid; 1H NMR (300 MHz, CDCl3) δ 1.69-1.88 (m, 5H), 1.96-2.04 (m, 1H), 2.88 (s, 2H), 6.91 (d, J=9.0 Hz, 1H), 7.38 (d, J=6.6 Hz, 1H), 7.76 (s, 1H).

1. temperatureThe reaction mixture was heated
2. temperatureto reflux under nitrogen for 14 h
3. customThe solvent was evaporated under reduced pressure
4. customthe residue obtained
5. extractionThe mixture was extracted with chloroform (3×100 ml)
6. washThe combined organic extracts were washed with water (100 ml), brine (50 ml)
7. dry with materialdried over anhydrous sodium sulfate
8. customThe residue obtained
9. customafter evaporation of the solvent
10. customwas purified by silica gel column chromatography

ORD record

ord-ea9a6d0b3b234dd99af7df330ae43b9f

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08492568B2