Diisopropylethylamine → 1-(4-aminopiperidin-1-yl)-3-methoxypropan-1-one

3-Methoxypropanoic acid (225 μL, 2.40 mmol) was added to a solution of 4-(N-Boc-amino)-piperidine (400 mg, 2.00 mmol) in methylene chloride (25 mL) at room temperature. N,N-diisopropylethylamine (1.30 mL, 7.49 mmol) and propylphosphonic anhydride (1.78 mL, 50 wt. % in ethyl acetate, 3.00 mmol) was added, and the solution was stirred for 4.5 h. The reaction mixture was concentrated and partitioned between ethyl acetate (5 mL) and water (5 mL). The organic portion was washed with 0.2M HCl (2 mL), sat. Sodium bicarbonate (5 mL) and brine (5 mL). The solution was then dried over sodium sulfate and concentrated to a white solid. This solid was taken up in methylene chloride (6 mL), and trifluoroacetic acid (3 mL) was added at room temperature. After 1 h the solution was concentrated. The resulting solid was dissolved in methylene chloride (2 mL) and 1M sodium hydroxide (1 mL). This mixture was extracted with methylene chloride (4×2 mL) and ethyl acetate (4×2 mL). The combined organic extracts were dried over sodium sulfate and concentrated to give 135 mg of the title compound, 1-(4-aminopiperidin-1-yl)-3-methoxypropan-1-one (36% over two steps). 1H NMR (300 MHz, CD3OD) δ 4.51-4.41 (m, 1H), 4.03-3.93 (m, 1H), 3.64 (d, J=6.3 Hz, 2H), 3.32 (s, 3H), 3.17-3.05 (m, 1H), 2.96-2.83 (m, 1H), 2.75-2.55 (m, 3H), 1.99-1.80 (m, 2H), 1.40-1.14 (m, 2H).

1. concentrationThe reaction mixture was concentrated
2. custompartitioned between ethyl acetate (5 mL) and water (5 mL)
3. washThe organic portion was washed with 0.2M HCl (2 mL), sat. Sodium bicarbonate (5 mL) and brine (5 mL)
4. dry with materialThe solution was then dried over sodium sulfate
5. concentrationconcentrated to a white solid
6. additiontrifluoroacetic acid (3 mL) was added at room temperature
7. concentrationAfter 1 h the solution was concentrated
8. dissolutionThe resulting solid was dissolved in methylene chloride (2 mL)
9. extractionThis mixture was extracted with methylene chloride (4×2 mL) and ethyl acetate (4×2 mL)
10. dry with materialThe combined organic extracts were dried over sodium sulfate
11. concentrationconcentrated

ORDレコード

ord-194888f940d14b2e8215f7c19ad94cb1

出典データセット

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08591943B2