2-Thiophenecarboxylic acid → 1-(Thiophene-2-carbonyl)piperidin-4-one

4-piperidone hydrochloride monohydrate (0.32 g, 2.1 mmol) was dissolved in DCM (7 ml), and to this was added MP-Carbonate resin (0.8 g). This was stirred at room temperature for 2 h. Separately, 2-thiophenecarboxylic acid (0.32 g, 2.52 mmol), N,N-4-dimethylaminopyridine (cat.), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 g, 6.3 mmol) and TEA (0.25 ml) were dissolved in DCM (7 ml) and stirred at room temperature for 2 h. The 2 reaction mixtures were then combined and stirred at room temperature for 18 h. The resulting solution was then filtered and washed with HCl (1M), sodium bicarbonate then brine. The organic layers were combined and dried over MgSO4 and evaporated to dryness. The crude mixture was purified using flash chromatography (0-100% ethyl acetate in hexane), to yield a white solid. 220 mg, (56%), mp. 81-83° C., LCMS tr=2.29 min (50% MeOH and 50% water at 0.5 ml/min), m/z M+H 210.11, HPLC tr=1.89 min (Isocratic 90% acetonitrile and 10% water at 1.0 ml/min), 100%, 1HNMR (CDCl3, 270 MHz) δ 2.47 (4H, t, J=6.2 Hz, CH2), 3.94 (4H, t, J=6.4 Hz, CH2), 7.00 (1H, dd, J=3.5, 4.9 Hz, ArH), 7.31 (1H, dd, J=1.2, 3.7 Hz, ArH), 7.43 (1H, dd, J=1.2, 4.9 Hz, ArH).

1. stirringstirred at room temperature for 2 h
2. customThe 2 reaction mixtures
3. stirringstirred at room temperature for 18 h
4. filtrationThe resulting solution was then filtered
5. washwashed with HCl (1M), sodium bicarbonate
6. dry with materialdried over MgSO4
7. customevaporated to dryness
8. customThe crude mixture was purified
9. customto yield a white solid

ORD record

ord-15da546861524ebd8445979588ec85c2

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08119627B2