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

Temperature

0 °C

In a separate reaction flask, to a stirred solution of gabapentin (1.8 g, 10 mmol) and triethylamine (4.3 mL, 31 mmol) in dichloromethane (100 mL) at 0° C. under nitrogen atmosphere, was added dropwise a solution of chlorotrimethylsilane (2.6 mL, 21 mmol) in dichloromethane (10 mL). After stirring for 30 min at 0° C., 2(R)-acetoxycyclopent-1(R)-yl chloroformate was added dropwise into the reaction mixture. The resulting mixture was stirred at 0° C. for 2 h and then at room temperature for 2 h (monitored by TLC). The reaction mixture was then concentrated in vacuo and the resulting residue was poured into cold water (50 mL), acidified to about pH 5.0 using 0.1 N HCl, then extracted using ethyl acetate (2×50 mL). The combined extracts were washed with brine (40 mL), dried over MgSO4 and concentrated in vacuo. The crude product was purified using flash chromatography on silica gel using hexane/ethyl acetate (2:1) as eluant to afford 2.0 g (84%) of compound 48 as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 1.31-1.78 (14H, m); 2.03-2.04 (5H, m); 2.31 (2H, s); 3.20 (2H, t, J=6.4 Hz); 5.07-4.97 (2H, m), 5.20 (1H, broad s). MS (ESI): m/z=340.25 (M−H−).

1. customIn a separate reaction flask
2. stirringThe resulting mixture was stirred at 0° C. for 2 h
3. waitat room temperature for 2 h (monitored by TLC)
4. concentrationThe reaction mixture was then concentrated in vacuo
5. additionthe resulting residue was poured into cold water (50 mL)
6. extractionextracted
7. washThe combined extracts were washed with brine (40 mL)
8. dry with materialdried over MgSO4
9. concentrationconcentrated in vacuo
10. customThe crude product was purified

ORD record

ord-23fe462518cb4b978e6228617c00a625

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07868041B2