SnCl4/Sn catalyzed chemoselective reduction of glycopyranosyl azides for the synthesis of diversely functionalized glycopyranosyl chloroacetamides

Article abstract of DOI:10.1016/j.tetlet.2013.07.110

A method for the chemoselective reduction of glycopyranosyl azides using SnCl₄ and tin metal as the reducing agent followed by in situ chloroacetylation of the synthesized glycopyranosyl amine was developed. This reaction is applicable to diversely functionalized glycopyranosyl azides for the synthesis of glycopyranosyl chloroacetamides.

Full text of DOI:10.1016/j.tetlet.2013.07.110

Tetrahedron Letters 54 (2013) 5361–5365
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
SnCl4/Sn catalyzed chemoselective reduction of glycopyranosyl
azides for the synthesis of diversely functionalized glycopyranosyl
chloroacetamides
⇑
Laxminarayan Sahoo , Anadi Singhamahapatra, Katuri J. V. Paul, Duraikkannu Loganathan
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A method for the chemoselective reduction of glycopyranosyl azides using SnCl4 and tin metal as the
reducing agent followed by in situ chloroacetylation of the synthesized glycopyranosyl amine was devel-
oped. This reaction is applicable to diversely functionalized glycopyranosyl azides for the synthesis of
glycopyranosyl chloroacetamides.
Received 2 May 2013
Revised 17 July 2013
Accepted 20 July 2013
Available online 27 July 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Glycopyranosyl azide
In situ reduction
Chloroacetylation
Functionalized glycoconjugates
Chemoselective organic transformations are useful tools for the
development of new methods in the synthesis of chemical ligating
agents. With enormous progress in the area of chemical biology,
there is a need to develop new methods to synthesize diversely
functionalized biomolecules using orthogonal chemical ligation
and automated chemical synthesis. Carbohydrates, with their
unparalleled structural diversity, can be used for the synthesis of
multifunctional chemical ligating agents.1 The huge range of bio-
logical applications of carbohydrates, as extensively studied in
the area of Glycobiology, further intensifies the need to develop
new strategies for the synthesis of diversely functionalized, carbo-
hydrate based chemical ligating agents.2 As part of the cell surface
complex biopolymers, sugars are connected to a wide variety of
biomolecules (e.g., protein, lipid, etc.) through diverse linkages.
The glycan part of these glycoconjugates (e.g., glycoproteins, glyco-
lipids), plays vital roles in numerous biological recognition pro-
cesses such as immune response.3,4 Thus, the development of
innovative and improved synthetic strategies for the rapid access
to diversely functionalized synthetic glycoconjugates is required
for the discovery of new therapeutics. Suitably protected or func-
tionalized glycosyl chloroacetamides have been used as important
building blocks for the synthesis of complex glycoconjugates. In our
earlier reports, suitably protected glycopyranosyl chloroacetamides
have been used for the synthesis of glycolipids5 and chemical ligat-
ing agents such as per-O-acetylated glycopyranosyl iodoaceta-
mides and per-O-acetylated glycopyranosyl azidoacetamides.6
Per-O-acetylated glycopyranosyl iodoacetamides are used for the
synthesis of glycoamino acids7 whereas per-O-acetylated glycopyr-
anosyl azidoacetamides are used for the synthesis of triazole linked
aromatic glycoconjugates8 and glycolipids.9 In the literature, suit-
ably protected glycopyranosyl chloroacetamide was used as accep-
tor in glycosylation reaction, followed by conversion of the
chloroacetamide to aminoacetamide which was used as a linker
for the synthesis of complex glycoconjugates.10 Earlier methods
for the synthesis of glycopyranosyl chloroacetamide involve con-
version of free sugar to the corresponding amine followed by chlo-
roacetylation.11 The yield of this reaction is low due to the
instability of the sugar amine. Other commonly used method for
the synthesis of glycosyl chloroacetamide involves in situ conver-
sion of sugar azide to amine using H2 in presence of Pd/C as the cat-
alyst, followed by chloroacetylation of the amine.6 Though Pd/C is
an efficient catalyst, it is expensive, and pyrophoric has limited
applications in the presence of functional groups such as benzyl,
double, or triple bond. Other palladium based catalysts like Lind-
lar’s catalyst have been used in the azide reduction only to a lim-
ited extent,12 as functional groups like triple bond are not stable
under this condition. Use of Staudinger reaction13–16 for the con-
version of sugar azide to amide in carbohydrate literature is hin-
dered due to lack of ready availability of the reagents and
sluggish reaction in some cases. As an alternative method, molyb-
denum based catalyst [BnNEt3]2MoS4 has also been used for the
⇑
Corresponding author. Tel.: +91 44 22575221, mobile: +91 9380820326; fax:
+91 44 22570509.
E-mail address: laxminarayanchem@gmail.com (L. Sahoo).
Deceased on 9th February, 2013.
z
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.07.110

5362
L. Sahoo et al. / Tetrahedron Letters 54 (2013) 5361–5365
reduction of sugar azide to amine.17 In the literature of organic
synthesis, SnCl2 is routinely used for the reduction of nitrate,18
nitrile19, and azide.20 SnCl2 was also used in stoichiometric amount
for the reduction of glycosyl azide to glycosylamine with a low
yield of 52%.21 The low yield may be due to the instability of glyco-
syl amine and highly hygroscopic nature of SnCl2. Here, in this
present work, a novel one-pot synthesis of diversely functionalized
glycopyranosyl chloroacetamides has been described, where cata-
lytic amount of SnCl4 reacts with tin metal to generate SnCl2,
which effectively converts glycopyranosyl azides to the corre-
sponding amines followed by in situ chloroacetylation.
OAc
OAc
SnCl4/ Sn,
O
O
chloroacetic anhydride
AcO
AcO
H
N
AcO
AcO
1
+
solvent, rt, 24 h
Cl
OAc
OH
OAc
O
Scheme 2. Reductive chloroacetylation of glucopyranosyl azide using different
solvents.
OAc
OAc
SnCl4/ Sn,
chloroacetic anhydride
O
O
AcO
AcO
H
N
AcO
AcO
1
+
solvent, rt, 24 h
Cl
OAc
OH
OAc
O
As a part of our work, different tin salts were tried as economical
and mild reagent system for the one pot reductive chloroacetylation
of glycopryranosyl azide to glycopyranosyl chloroacetamide. In the
literature, SnCl2 is very well-known for the reduction of azide to
amine.11 Per-O-acetylated glucopyranosyl azide (1, 1 mmol) was
treated with anhydrous SnCl2 (1 mmol) in dry methanol in the pres-
ence of chloroacetic anhydride (1.1 mmol) (Scheme 1).
Scheme 3. Reductive chloroacetylation of glucopyranosyl azide using different
chloroacetylating agent.
Table 2
Reductive chloroacetylation using SnCl4/Sn in different solvents
The 1H NMR of the crude product showed the presence of three
Solvent
13 (% yield)
14 (% yield)
compounds 2,3,4,6-tetra-O-acetylated-
60%) along with 40% of the desired product, per-O-acetylated
b- -glucopyranosyl chloroacetamide (14). The yield of the desired
chloroacetamide increased from 40% to 50% by using Sn(II) acetate
along with tin metal. This initial result led us to replace the hygro-
scopic Sn(II) salts with catalytic amount of SnCl4 (10 mol %, 1 M
solution in DCM) along with tin metal to generate Sn(II) in situ.
The mixture of SnCl4 (10 mol %) with tin metal works as good as
Sn(OAc)2/Sn mixture and the desired chloroacetamide was
obtained in 50% yield (Table 1).
a/b-D-glucopyranose (13,
DCM
CH3CN
DMF
DCM + DMF (9:1)
0
0
50
25
0
0
50
75
D
Table 3
Reductive chloroacetylation of glucopyranosyl azide using different chloroacetylating
agent
Acetylating agent
13 (% yield)
14 (% yield)
The formation of product 13 is due to the hydrolysis of the
unstable intermediate per-O-acetylated-b-D-glucopyranosyl amine
in methanol. For this reason, a series of solvents other than meth-
anol were screened for this reaction using SnCl4 (10 mol %)/Sn as
the reducing agent and chloroacetic anhydride as the acylating
agent (Scheme 2).
ClCH2COOH
0
25
20
0
100
75
80
(ClCH2CO)2O
DCC + ClCH2COOH
ClCH2COCl
100
The reaction did not work in aprotic solvents like acetonitrile,
dichloromethane (DCM) and unreacted per-O-acetylated glucopyr-
anosyl azide was recovered in both the cases. In dry DMF, the yield
of compound 14 was only 50%. Then different solvent combina-
tions were tried and DCM with dimethylformamide (DMF) (9:1)
was found to be the most efficient solvent system resulting in
the formation of 75% of the required chloroacetamide 14 (Table 2,
Scheme 3).
To improve the yield of the desired product further by using
more reactive chloroacetylating agent, a set of chloroacylating
agents were screened for the reaction with the best possible
combination of reducing agent and solvent system. Unlike
Staudinger reaction, chloroacetic acid was found to be unreac-
tive in case of the SnCl4/Sn reagent system and 2,3,4,6-tetra-O-
acetyl- /b- -glucopyranose 13 was obtained as the only product.
a
D
Dicyclohexylcarbodiimide (DCC) activated chloroacetic acid gave
a better yield of chloroacetamide 14 (80%), but when chloroace-
tyl chloride was used as the acylating agent, the glycosyl azide
was fully converted to the corresponding chloroacetamide 14
without the formation of corresponding C-1 hydroxy derivative
13 (Table 3).
From the above results, the best possible combination was
found to be SnCl4 (10 mol %)/Sn as the reducing agent in a mixture
of DCM and DMF (9:1) as the solvent and chloroacetyl chloride as
the chloroacylating agent (Scheme 4).
A plausible mechanism of the reaction was proposed where
Sn(IV) (from SnCl4) reacts with tin metal to generate Sn(II) in situ.
This Sn(II) acts as the reducing agent for the sugar azide and itself
gets oxidized to Sn(IV). Sn(II) is regenerated again in the system by
reaction of Sn(IV) and tin. This way only catalytic amount of SnCl4 re-
duces the sugar azide in the presence of tin metal.
To examine the utility of this reaction, a series of diversely pro-
tected glycosyl azides (Table 4) were reacted in the standard reac-
tion condition where SnCl4 (10 mol %) with tin metal in a mixture
OAc
OAc
Sn reagent,
O
O
H
N
AcO
AcO
AcO
AcO
chloroacetic anhydride
+
1
Cl
OH
OAc
OAc
13
dry MeOH, rt, 24 h
O
14
Scheme 1. Reductive chloroacetylation of glucopyranosyl azide using different tin
reagents.
SnCl4 /Sn,
OAc
ClCH2COCl
Table 1
O
1
H
N
AcO
AcO
Reductive chloroacetylation using different Sn reagents
dry DCM / DMF (9 : 1)
rt, 24 h
Cl
OAc
Sn reagent
13 (% yield)
14 (% yield)
O
14
SnCl2
Sn(OAc)2/Sn
SnCl4/Sn
60
50
50
40
50
50
Scheme 4. Reductive chloroacetylation of glucopyranosyl azide under standard
reduction condition.

L. Sahoo et al. / Tetrahedron Letters 54 (2013) 5361–5365
5363
Table 4
Reductive chloroacetylation of glycopyranosyl azide
Sugar azide
Product
Yield (%)
OAc
OAc
O
O
AcO
AcO
N3
AcO
NHCOCH2Cl
87
AcO
OAc
OAc
1
14
OAc
OAc
O
O
AcO
AcO
AcO
AcO
80
N3
NHCOCH2Cl
NHCOCH2Cl
2
NHAc
O
NHAc
O
15
AcO
AcO
AcO
AcO
90a
N3
OAc
OAc
3
16
OAc
OAc
OAc
O
OAc
O
85
80
AcO
N3
AcO
NHCOCH2Cl
NHCOCH2Cl
OAc
OAc
4
17
OAc
O
OAc
O
AcO
AcO
AcO
AcO
AcO
N3
AcO
18
5
OAc
O
OAc
O
AcO
AcO
AcO
AcO
AcO
85a
AcO
NHCOCH2Cl
OAc
6
19
OAc
N3
OAc
OAc
O
O
O
O
AcO
AcO
AcO
AcO
O
O
80
80
AcO
N3
AcO
NHCOCH2Cl
OAc
OAc
OAc
OAc
20
OBz
OBz
O
O
BzO
BzO
BzO
BzO
N3
N3
N3
NHCOCH2Cl
OBz
OBz
21
8
OPiv
OPiv
O
O
OPiv
OPiv
OPiv
OPiv
90
NHCOCH2Cl
OPiv
OPiv
9
22
OBn
OBn
O
O
BnO
BnO
BnO
BnO
NHCOCH2Cl
50
95
75
OBn
OBn
10
23
OBn
O
Ph
O
O
O
BnO
BnO
NHCOCH2Cl
O
O
N3
OBn
NHAc
O
11
23
O
O
O
O
Ph
O
N3
O
NHCOCH2Cl
NHAc
NHAc
12
24
a
Mixture of
a and b isomers in the ratio 1:1.
of DCM and DMF (9:1) was used as the reducing agent and chloro-
acetyl chloride as the chloroacylating agent (Scheme 5).22 In case of
2-deoxy-2-acetamido glucopyranose (GlcNAc, 2), galactose (4),
b-mannose (5), and cellobiose (7); b-chloroacetamides (15, 17,
18, and 20) were obtained as the major product with small amount
of hydrolyzed C-1 OH derivative (Table 4). For xylose (3), the reac-
tion gave rise to a mixture of chloroacetamides. Analytically pure
mixture of a as well as b chloroacetamide (19) was obtained. The
formation of the compounds was confirmed by 1H NMR, 13C
NMR, and ESI-MS spectra. This is the first report on the synthesis
of per-O-acetylated-a-D-glycosyl chloroacetamide.
After examining different per-O-acetylated sugar azides, the
scope of this methodology was extended to other protecting
groups. In case of per-O-benzoyl (8), per-O-pivoloyl (9), and per-
O-benzyl (10) glucopyranosyl azides, corresponding chloroaceta-
mides (21–23) were obtained in good to excellent yield and the
protecting groups were intact under the reaction condition.
2,3,4-tri-O-acetyl-b-
obtained after recrystallization. When the reaction was performed
with 2,3,4,6-tetra-O-acetyl- -mannopyranosyl azide (6),
D-xylopyranosyl chloroacetamide (16) was
a
-D
a

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L. Sahoo et al. / Tetrahedron Letters 54 (2013) 5361–5365
and Industrial Research (CSIR), New Delhi for the award of Senior
Research Fellowships.
SnCl4 /Sn,
O
O
H
N
Chloroacetyl chloride
N3
(RO)n
(RO)n
Cl
dry DCM / DMF (9 : 1),
rt, 24 h
O
Supplementary data
R = Protecting group
Supplementary data (1H and 13C NMR spectral data of new com-
pounds) associated with this article can be found, in the online ver-
sion, at http://dx.doi.org/10.1016/j.tetlet.2013.07.110.
Scheme 5. Reductive chloroacetylation of glycopyranosyl azide under standard
reaction condition.
1. PhCH(OMe)2,PTSA,
DMF,0 oC - RT, 4 h
OH
References and notes
O
Ph
O
O
O
HO
HO
N3
O
N3
1. Lepenies, B.; Yin, J. A.; Seeberger, P. H. Curr. Opin. Struct. Biol. 2010, 14, 404.
2. Dwek, R. A. Chem. Rev. 1996, 96, 683.
2. NaH, Dry DMF
Br
0 oC - RT, 24 h
NHAc
NHAc
11
2a
3. Van Kooyk, Y.; Rabinovich, G. A. Nat. Immunol. 2008, 9, 593.
4. Rabinovich, G. A.; Toscano, M. A. Nat. Rev. Immunol. 2009, 9, 338.
5. Paul, K. J. V.; Sahoo, L.; Loganathan, D. Trends Carbohydr. Res. 2012, 4, 1.
6. Paul, K. J. V.; Sahoo, L.; Sorna, V.; Loganathan, D. Trends Carbohydr. Res. 2010, 2,
21.
7. Paul, K. J. V.; Sahoo, L.; Loganathan, D. Tetrahedron Lett. 2010, 51, 5713.
8. Alexacou, K. M.; Hayes, J. M.; Tiraidis, C.; Zographos, S. E.; Leonidas, D. D.;
Chrysina, E. D.; Archontis, G.; Oikonomakos, N. G.; Paul, K. J. V.; Varghese, B.;
Loganathan, D. Proteins: Struct., Funct., Bioinf. 2008, 71, 1307.
9. Paul, K. J. V.; Loganathan, D. Tetrahedron Lett. 2008, 49, 6356.
10. Barclay, W. S.; Jones, I. M.; Osborn, H. M. I.; Phillipson, L.; Ren, J.; Taleveraa, G.
A.; Thompsona, C. I. Bioorg. Med. Chem. 2007, 15, 4038.
11. Aich, U.; Lakshmanan, T.; Varghese, B.; Loganathan, D. J. Carbohydr. Chem. 2003,
22, 891.
OH
O
O
NaH, Dry DMF
O
HO
HO
O
N3
O
N3
Br
NHAc
NHAc
2a
0 oC - RT, 24 h
12
Scheme 6. Synthesis of alkyl or alkyne functionalized 2-acetamido-2-deoxy-b-D-
glucopyranosyl azide.
12. Witte, M. D.; De Descals, C. V.; Lavoir, S. V. P.; Van der Florea, B. I.; Marel, G. A.;
Overkleeft, H. S. Org. Biomol. Chem. 2007, 5, 3690.
13. Nyffeler, P. T.; Liang, C. H.; Koeller, K. M.; Wong, C. H. J. Am. Chem. Soc. 2002,
124, 10773.
In addition to different protecting groups, the application of this
reagent system was examined for diversely functionalized sugar
azides containing allyl, propargyl, and bezylidene functionality.
For the synthesis of allyl and benzylidene group containing sugar
14. García-López, J. J.; Santoyo-González, F.; Vargas-Berenguel, A. Synlett 1997,
265.
´
´
15. Vargas-Berenguel, A.; Ortega-Caballero, F.; Garcıa-Lopez, J. J.; Gimenez-
´
azide, 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-b-D-glucopyranosyl
Mart´ınez, J. J.; Garcıa-Fuentes, L.; Ortiz-Salmero´n, E.; Santoyo-Gonza´lez, F.
Chem. Eur. J. 2002, 8, 812.
´
azide (2) was de-O-acetylated using catalytic amount of sodium
methoxide in methanol to obtain the free glycosyl azide 2a. Com-
pound 2a was reacted with 2,2-dimethoxy benzaldehyde in the
presence of p-toluenesolfonic acid (p-TSA) in dry DMF and the
crude product obtained was alkylated using allyl bromide in the
presence of sodium hydride in dry DMF to give 2-deoxy-2-acetam-
16. García-López, J. J.; Santoyo-González, F.; Vargas-Berenguel, A.; Giménez-
Martínez, J. J. Chem. Eur. J. 1999, 5, 1775.
17. Sridhar, P. R.; Prabhu, K. R.; Chandrasekaran, S. J. Org. Chem. 2003, 68, 5261.
18. Bellamy, F. D.; Ou, K. Tetrahedron Lett. 1984, 25, 839.
19. Willium, J. W. Org. Synth. 1955, coll. Vol. 3, 626.
20. Maiti, S. N.; Singh, M. P.; Micetich, R. G. Tetrahedron Lett. 1986, 27, 1423.
21. Hayes, P. Y.; Ross, B. P.; Thomas, B. G.; Toth, I. Bioorg. Med. Chem. 2006, 14, 143.
22. Reduction of glycosyl azide and in situ chloroacetylation using SnCl4/Sn (14–
25): General procedure: Protected glycosyl azide (1 mmol) was taken in a
100 mL two-necked round bottom flask along with 2–4 tin bits (0.5 g) and
anhydrous sodium sulfate (10 mg). To this, 9 mL of dry DCM was added
followed by dry DMF (1 mL) and chloroacetyl chloride (0.1 mL, 1.2 mmol). The
reaction was initiated by adding SnCl4 (0.1 mmol) and was allowed till
complete consumption of glycosyl azide. The reaction was then continued for
another 6 h. The reaction mixture was first filtered, then diluted with 50 mL of
DCM, and washed with distilled water (3 Â 30 mL). The organic layer was dried
over sodium sulfate and concentrated to dryness to give the title compound in
good to excellent yield.
ido-3-O-allyl-4,6-O-benzylidene-b-D-glucopyranosyl azide (11) in
65% overall yield after purification by column chromatography
(Scheme 6).23
For the synthesis of per-O-propargylated glycosyl azide (12),
compound 2a was propargylated using propargyl bromide in the
presence of sodium hydride in dry DMF to give 2-acetamido-2-
deoxy-3,4,6-tri-O-acetyl-b-D-glucopyranosyl azide (12) in 70%
overall yield (Scheme 6).24
Both the alkene and alkyne functionalized sugar azides were re-
acted with chloroacetyl chloride in the presence of Sn/SnCl4 as
mentioned earlier. The desired products (24 and 25) were obtained
in good to excellent yield in the presence of functional groups such
as alkene, alkyne, and acetal (Table 4).
In conclusion, an efficient and economical method for the
reduction of diversely protected or functionalized sugar azides to
amines followed by in situ chloroacetylation was developed. Other
advantages of this methodology like the selective synthesis of gly-
23. Synthesis of 2-acetamido-2-deoxy-3-O-allyl-4,6-O-(phenylmethylene)-b-
glucopyranosyl azide (11). 2-Acetamido-2-deoxy-3,4,6-tri-O-acetyl-b-
D
-
-
D
glucopyranosyl azide (2, 372 mg,1 mmol) was deacetylated by using catalytic
amount of NaOMe in methanol (5 mL). After complete deprotection, indicated by
TLC, the reaction was quenched by IR 120 H+ resin. The reaction mixture was
filtered and concentrated to dryness. The crude product was used for the next
step without any further purification. 2-(Acetamido)-2-deoxy-b-D-
glucopyranosyl azide (2a, 246 mg, 1 mmol) was dissolved in 10 mL of dry DMF
and 2 mL of benzaldehyde dimethyl acetal and a catalytic amount of p-TSA were
added to this and the reaction mixture was heated to 50 °C. After completion of
the reaction, the reaction mixture was dried under vacuum. NaH (48 mg,
2 mmol) was taken in a two-necked round bottom flask under nitrogen. Dry DMF
(5 mL) was added to this and the suspension was cooled to 0 °C. Then 2-deoxy-2-
copyranosyl a-chloroacetamide are yet to be explored. This meth-
odology can complement the existing method of reduction of sugar
azides, functionalized with sensitive functional groups like alkyne,
allyl, or benzelidene acetal. These diversely functionalized and
multivalent glycopyranosyl chloroacetamides will be useful for
the synthesis of complex glycoconjugates like glycodendrimers,
glycopeptides, and glycolipids.
acetamido-4,6-O-(phenylmethylene)-b-D-glucopyranosyl azide obtained in the
above reaction, taken in 5 mL of dry DMF, was added to the reaction mixture and
was allowed to stir at that temperature for 30 min. Allyl bromide (0.2 mL,
2.3 mmol) was then added to the reaction mixture and the reaction was allowed
to come to room temperature. After completion of the reaction, monitored by
TLC, the reaction mixture was diluted with 50 mL of ethyl acetate, washed
several times with distilled water and finally by saturated sodium chloride
solution (30 mL). The organic layer was dried over sodium sulfate and
concentrated to dryness. The crude product was purified by column
chromatography (100–200 mesh silica gel, 1:1 ethyl acetate and hexane) to
give the title compound in 65% overall yield.
Acknowledgements
24. Synthesis of 2-acetamido-2-deoxy-3,4,6-tri-O-propargyl-b-D-glucopyranosyl
The authors thank Indian Institute of Technology Madras for
NMR and ESI-MS facility. L.N.S. is thankful to the University Grants
Commission (UGC), New Delhi for the award of a Senior Research
Fellowship. A.S. and J.V.P. are thankful to the Council of Scientific
azide (12). NaH (144 mg, 6 mmol) was taken in a two-necked round bottom
flask under nitrogen. 5 mL of dry DMF was added to this and the suspension
was cooled to 0 °C. 2-Acetamido-2-deoxy-b-
D-glucopyranosyl azide (2a,
246 mg, 1 mmol), synthesized in the above procedure was added to this and

L. Sahoo et al. / Tetrahedron Letters 54 (2013) 5361–5365
5365
the reaction mixture was stirred at that temperature for 30 min. Propargyl
bromide (0.5 mL, 6.6 mmol) was then added to the reaction mixture and the
reaction was allowed to come to room temperature. After completion of the
reaction, 50 mL of ethyl acetate was added to this. The organic layer was
washed with distilled water (30 mL Â 5), dried over anhydrous sodium sulfate,
and concentrated to dryness. The crude product was purified by column
chromatography (100–200 mesh silica gel, 1:1 ethyl acetate and hexane) to
give the desired compound in 70% overall yield.