Gabapentin → 1-{{[(Cyclohexanon-2-yl)oxy]carbonyl}aminomethyl}-1-Cyclohexane Acetic Acid

温度

0 °C

To a stirred solution of gabapentin (2.56 g, 15 mmol) and chlorotrimethylsilane (3.7 mL, 30 mmol) in dichloromethane (25 mL) at 0° C. under nitrogen atmosphere was added triethylamine in portions. After having stirred for 15 min at 0° C. the chloroformate (45) was added dropwise into the reaction mixture. The mixture was stirred at 0° C. for 2 h and then at room temperature for 2 h (monitored by TLC). The reaction mixture was concentrated in vacuo and the residue was poured into cold water (50 mL) and then acidified to about pH 5.0 using 0.1 N HCl. The crude product was then extracted using ethyl acetate (2×50 mL). The combined extracts were washed with brine (40 mL), dried over MgSO4 and the solvent removed in vacuo. The crude product was dissolved in acetone (25 mL) and treated using Amberlyst-15 (11.0 g) for 1.5 h (monitored by LC/MS). The reaction mixture was filtered and the filtercake was washed with acetone (2×15 mL). The combined extracts were evaporated under reduced pressure and the residue was purified using prep-HPLC/MS method to provide 1.71 g (55% yield) of compound 46 as a white solid. 1H NMR (CDCl3, 400 MHz): 5.42 (1H, t), 5.12 (1H, m), 3.35-3.16 (2H, m), 2.39 (4H, m), 1.80-1.40 (16H, m). MS (ESI): m/z=310.27 (M−H−), and 312.28 (M+H+).

1. additionwas added dropwise into the reaction mixture
2. waitat room temperature for 2 h (monitored by TLC)
3. concentrationThe reaction mixture was concentrated in vacuo
4. additionthe residue was poured into cold water (50 mL)
5. extractionThe crude product was then extracted
6. washThe combined extracts were washed with brine (40 mL)
7. dry with materialdried over MgSO4
8. customthe solvent removed in vacuo
9. dissolutionThe crude product was dissolved in acetone (25 mL)
10. additiontreated
11. customfor 1.5 h
12. filtrationThe reaction mixture was filtered
13. washthe filtercake was washed with acetone (2×15 mL)
14. customThe combined extracts were evaporated under reduced pressure
15. customthe residue was purified

ORDレコード

ord-fdd03ef4245c44d2afc1c404162b4ec2

出典データセット

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07868041B2