Ammonia → (5S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-1-(6-methoxy-2-pyridinyl)-2-piperidinone

Temperature

140 °C

A mixture of (5S)-5-(3,4-d ichlorophenyl)-5-(1,3-d ioxolan-2-yl methyl)-2-piperidinone (WO 9807722) (4.7 g, 14.3 mmol), potassium carbonate (2.97 g, 21.4 mmol), copper (I) iodide (3.0 g, 15.7 mmol) and the bromide from preparation 7 (4.03 g, 21.4 mmol) in 1-methyl-2-pyrrolidinone (25 ml) was stirred at 140° C. for 4 hours, followed by 18 hours at room temperature. The cooled mixture was poured into 2N hydrochloric acid (100 ml), then treated with 0.88 ammonia (100 ml). This aqueous mixture was extracted with ethyl acetate (2×200 ml), the combined organic extracts were washed with water (50 ml), then brine (100 ml), dried (MgSO4) and evaporated under reduced pressure to give an oil. The crude product was purified by column chromatography on silica gel using an elution gradient of dichloromethane:methanol (100:0 to 98:2). The resulting product was dissolved in ether (100 ml), the solution washed with water (5×20 ml), dried (MgSO4) and evaporated under reduced pressure to afford the title compound as a foam, 2.85 g.

1. waitfollowed by 18 hours at room temperature
2. extractionThis aqueous mixture was extracted with ethyl acetate (2×200 ml)
3. washthe combined organic extracts were washed with water (50 ml)
4. dry with materialbrine (100 ml), dried (MgSO4)
5. customevaporated under reduced pressure
6. customto give an oil
7. customThe crude product was purified by column chromatography on silica gel using an elution gradient of dichloromethane:methanol (100:0 to 98:2)
8. dissolutionThe resulting product was dissolved in ether (100 ml)
9. washthe solution washed with water (5×20 ml)
10. dry with materialdried (MgSO4)
11. customevaporated under reduced pressure

ORD record

ord-696e8e223dd741088c8c2b67219c19ee

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07060836B2