Chemical Papers
method to prepare 5-alkyl or vinyl-2-pyrrolidinone deriva-
tives. In addition, introduction of K2CO3 in the synthesis of
5-vinyl-2-pyrrolidinone makes the whole process simple,
eco-friendly and cost efective.
D2O): 8.96, 25.79, 28.43, 30.19, 56.62, 181.15; GCMS
(m/z): 111;
Synthesis of vigabatrin (1)
To a stirred solution of potassium hydroxide (12.6 g,
0.22 mol) in H2O (23 mL), 5-vinyl-2-pyrrolidinone (25 g,
0.22 mol) was added. The reaction mass was warmed and
stirred for 2 h under refux. The reaction mixture was diluted
with isopropanol (200 mL) after cooling to 25–30 °C. To this
solution, acetic acid (13.5 g, 0.22 mol) was added portion
wise over 30 min. The slurry was stirred for 2 h at 20–30 °C
and subsequently for 2 h at 0–5 °C. The precipitated product
was collected by fltration and dried to aford 1 (13 g, 74%)
General information
Unless otherwise stated, all melting points were uncorrected
and were determined on a Reichert Thermopan apparatus.
The purity/impurity ratios of compounds 1 and 2 were deter-
mined by Waters Alliance 2695 separations module system
and 2487 dual λ absorbance detector. HPLC measurements
were run on Sperisorb C6, 250 mm×4.6 mm, 5 μm (Make:
Waters) and Partsil 10 SCX, 250 mm, 4.6 mm, 10 μm
(Make: Hi Chrom) connected in series at 25 °C with fow
1
as an of-white solid. Purity by HPLC: 99.67%; H NMR
(300 MHz, D2O): 0.97–1.02 (t, 3H), 1.63–1.77 (m, 2H),
1.85–1.97 (m, 2H), 2.31–2.36 (m, 2H), 3.20–3.25 (t, 1H);
13C NMR (300 MHz, D2O): 31.58, 36.08, 56.64, 123.76,
135.6, 184.02; HRMS (ESI) calculated for C6H13NO2
(M+H)+ 130.0868, found: 130.0888;
rate of 1.0 ml/min and the run time of 60 min. 1H and 13
C
NMR spectra were recorded by a Bruker Avance 300 MHz
and Varian 500 MHz spectrometer using TMS as internal
standard in D2O and DMSO-d6. The 1H chemical shift val-
ues were reported in the δ scale relative to TMS (δ 0.00)
and the 13C chemical shift values were given relative to
DMSO-d6 and D2O as internal standards. The IR spectra
were recorded as KBr pellets using Perkin Elmer Spectrum
One Fourier Transform (FT) IR spectrophotometer. High-
resolution mass spectral (HRMS) analyses were performed
using the electro spray ionization (ESI) method on Xevo G2
QTOF mass spectrometer. All raw materials were purchased
from commercial sources and used without purifcation.
Supplementary information Supplementary information fle
containing 1H, 13C NMR, HRMS and HPLC chromatogram
of compound 1; 1H NMR, GCMS and HPLC chromatogram
Acknowledgements The authors gratefully acknowledge the man-
agement of Aurobindo Pharma Limited for supporting this work. The
authors highly appreciate the co-operation of Chemical Research and
Analytical research departments.
Experimental
Compliance with ethical standards
Synthesis of 5‑vinyl‑2‑pyrrolidinone (2)
Conflict of interest The authors declare no confict of interest.
To a stirred -15 to -10 °C solution of 5-ethoxy-2-pyrroli-
dinone (8) (25 g, 0.19 mol) in tetrahydrofuran (150 mL),
potassium carbonate (6.7 g, 0.04 mol) was added under
nitrogen atmosphere. To this suspension, vinyl magnesium
bromide (1 M, 297 mL, 0.28 mol) was added portion wise
over 1 h. The heterogeneous reaction mixture was warmed
and stirred under a gentle refux for 2 h. After cooling the
reaction mixture to 0 °C, a mixture of H2O (250 mL) and
acetic acid (50 mL) was added cautiously by maintaining the
temperature between 0–20 °C. The insolubles were removed
through hyfo bed fltration. The volatiles in the fltrate
were concentrated and the residue was extracted with DCM
(250 mL). The organic layer was separated and evaporated
under reduced pressure to aford (RS)-5-vinyl-2-pyrrolidi-
none (17.5 g, 81%) as dark brown colour syrup. Purity by
HPLC: 97.97%; 1H NMR (300 MHz, D2O): 1.60–1.70 (m,
1H), 2.08–2.24 (m, 3H), 4.00–4.06 (m, 1H), 5.02–5.18 (m,
1H), 5.75–5.86 (m, 1H), 7.83 (s, 1H); 13C NMR (300 MHz,
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