Reaction #339483

Reaction equation

chloroformate

2,2-Dimethoxycyclohex-1-yl Chloroformate

gabapentin

chlorotrimethylsilane

triethylamine

→

compound 46

Yield 55.0%

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

Yield 55.0%

Solvents

dichloromethane

Conditions

Workup

1. 1
   workup.ADDITIONwas added dropwise into the reaction mixture
2. 2
   workup.WAITat room temperature for 2 h (monitored by TLC)
3. 3
   ConcentrationThe reaction mixture was concentrated in vacuo
4. 4
   workup.ADDITIONthe residue was poured into cold water (50 mL)
5. 5
   ExtractionThe crude product was then extracted
6. 6
   WashThe combined extracts were washed with brine (40 mL)
7. 7
   Dryingdried over MgSO4
8. 8
   Otherthe solvent removed in vacuo
9. 9
   workup.DISSOLUTIONThe crude product was dissolved in acetone (25 mL)
10. 10
    workup.ADDITIONtreated
11. 11
    Otherfor 1.5 h
12. 12
    FiltrationThe reaction mixture was filtered
13. 13
    Washthe filtercake was washed with acetone (2×15 mL)
14. 14
    OtherThe combined extracts were evaporated under reduced pressure
15. 15
    Otherthe residue was purified

Procedure

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+).

Source