The Journal of Organic Chemistry
Note
was used as such for the next step without further purification due to
more polar nature of acid compound (R)-8 (1.26 g, 78% yield
determined by 1H NMR). The analytical sample was obtained by
preparative chromatography on silica gel (CH2Cl2/MeOH, 9:1 v/v) as
ACKNOWLEDGMENTS
■
Y.G. thanks UGC, New Delhi for a research fellowship. S.K.P. is
thankful to Department of Science and Technology, New Delhi,
for generous funding of the project (Grant No. SB/FT/CS-178/
2011). We are grateful to Prof. Prakash Gopalan for his support
and encouragement.
yellow oil. [α]25 +66.5 (c 0.1, MeOH); IR (CH2Cl2) ν: 2896, 1775,
D
1
1699, 1604, and 1392 cm−1; H NMR (400 MHz, CDCl3) δ: 3.36 (s,
3H), 4.0 (m, 1H), 4.17 (t, J = 10.08 Hz, 1H), 5.17−5.19 (m, 1H), 7.7
(dd, 2H), 7.8 (dd, 2H), 8.05 (bs, 1H); 13C NMR (100 MHz, CDCl3) δ:
58.6, 60.5, 70.1, 119.0, 123.3, 128.6, 131.9, 133.8, 168.1, 171.2; HRMS
(ESI-TOF) m/z calcd for C12H11NO5Na [M + Na+] 272.050; found
272.053.
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To a crude acid (R)-8 (1.25 g, 5 mmol) in dry THF was added N-methyl
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2H), 7.27−7.3 (m, 5H), 7.2 (bs, 1H), 5.0 (m, 1H), 4.4 (m, 2H), 4.3 (t, J
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CH2Cl2/MeOH 9:1 v/v). The resulting crude was used as such for the
next step without further purification.
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The residue was then dissolved in dry toluene followed by addition of
Na2CO3 (1.3 g, 12.3 mmol). The reaction mixture was cooled to 0 °C
after which acetyl chloride (0.33 mL, 4.5 mmol) was slowly added and
the solution stirred at 5 °C for 1 h. After completion of the reaction, the
solid was filtered through a Celite pad and the solvent was evaporated in
vacuo. The crude product was purified by silica gel column
chromatography (CH2Cl2/MeOH 19:1 v/v) to afford 935 mg (91%)
yield of (R)-lacosamide 2 as white solid. [Rf = 0.47, CH2Cl2/MeOH 9:1
v/v]; mp 143−144 °C [Lit. 140−141 °C,5g 142−143 °C5h]; [α]25
D
+16.1 (c 1, MeOH) [Lit. +16.2 (c 1, MeOH),5g +16.1 (c 1.2, MeOH)5h];
IR (CH2Cl2) ν: 3054, 2928, 1650, 1529, 1372, 1264, and 1118 cm−1; 1H
NMR (400 MHz, CDCl3) δ: 7.24−7.68 (m, 5H), 6.86 (s, 1H), 6.54 (s,
1H), 4.5 (m, 1H), 4.4 (m, 2H), 3.80 (dd, J = 9.2, 4.1 Hz, 1H), 3.4 (m,
1H), 3.37 (s, 3H), 2.02 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 170.3,
169.9, 137.8, 128.7, 127.5, 127.4, 71.6, 59.0, 52.3, 43.5, 23.2.
ASSOCIATED CONTENT
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S
* Supporting Information
Copies of 1H and 13C NMR spectra of compounds 2 and 6−9,.
This material is available free of charge via the Internet at http://
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AUTHOR INFORMATION
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Corresponding Author
*Phone: +91-175-239-3832. Fax: +91-175-236-4498. E-mail:
Notes
The authors declare no competing financial interest.
C
J. Org. Chem. XXXX, XXX, XXX−XXX