P-Chloroacetophenone → HCID 86722009, compound

Temperature

-78 °C

A solution of 1-(4-chlorophenyl)ethanone (2.0 g, 12.9 mmol) in anhydrous THF was cooled in a dry ice acetone bath and treated with sodium hexamethyldisilazid (14.2 mL, 1M in THF, 14.2 mmol). The resulting solution was stirred for 1 h at −78° C. and a solution of tetrahydro-pyran-4-carbonyl chloride (1.92 g, 12.9 mmol) in THF was slowly added. The resulting solution was stirred for 30 min at −78° C., allowed to warm up to room temperature and stirred for 5 h. The reaction was quenched by adding 6N HCl and extracted with EtOAc (×3). The organic fractions were combined and washed with sat. NaCl, dried over Na2SO4 and evaporated under vacuum. The resulting residue was purified by silica-gel column chromatography to give 2 g (58%) of 1-(4-chlorophenyl)-3-(tetrahydro-2H-pyran-4-yl)propane-1,3-dione. 1-(4-chlorophenyl)-3-(tetrahydro-2H-pyran-4-yl)propane-1,3-dione 100 mg (0.375 mmol) and the free base of the corresponding hydrazine (1.1 equivalent) were dissolved in acetic acid and heated at 100° C. for 18 h. Acetic acid was removed under vacuum and the residue was purified by reverse phase HPLC.

1. stirringThe resulting solution was stirred for 30 min at −78° C.
2. temperatureto warm up to room temperature
3. stirringstirred for 5 h
4. customThe reaction was quenched
5. additionby adding 6N HCl
6. extractionextracted with EtOAc (×3)
7. washwashed with sat. NaCl
8. dry with materialdried over Na2SO4
9. customevaporated under vacuum
10. customThe resulting residue was purified by silica-gel column chromatography

ORD record

ord-1dc880b3fc974684a12ded9606e27564

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901314B2