Reaction #339485

Reaction equation

2(R)-acetoxycyclopent-1(R)-yl chloroformate

gabapentin

triethylamine

chlorotrimethylsilane

→

compound 48

Yield 84.0%

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

Yield 84.0%

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   OtherIn a separate reaction flask
2. 2
   workup.STIRRINGThe resulting mixture was stirred at 0° C. for 2 h
3. 3
   workup.WAITat room temperature for 2 h (monitored by TLC)
4. 4
   ConcentrationThe reaction mixture was then concentrated in vacuo
5. 5
   workup.ADDITIONthe resulting residue was poured into cold water (50 mL)
6. 6
   Extractionextracted
7. 7
   WashThe combined extracts were washed with brine (40 mL)
8. 8
   Dryingdried over MgSO4
9. 9
   Concentrationconcentrated in vacuo
10. 10
    OtherThe crude product was purified

Procedure

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−).

Source