General methods for synthesis of N-methyliminodiacetic acid boronates from unstable ortho-phenolboronic acids

Article abstract of DOI:10.1002/adsc.201301023

A range of N-methyliminodiacetic acid (MIDA) boronates of commercially available but unstable ortho-phenolboronic acid derivatives can be readily prepared through simple condensation between the corresponding phenolboronic acids and MIDA in the presence of molecular sieves. The resulting MIDA boronates are bench-top stable and display a remarkable stability even in DMSO solution at high temperature (>120°C) compared with their parent boronic acids. Moreover, the utility of the resulting MIDA boronate was successfully demonstrated in a cross-coupling reaction using the slow-release protocol to afford the cross-coupled product in much better yield compared with its parent boronic acid counterpart. In addition, an alternative, but more efficient, synthetic route for difficult-to-access ortho-phenol MIDA boronates has been developed through the MIDA boronate formation of methoxymethyl (MOM) protected ortho-phenolboronic acid, followed by deprotection of the MOM group with TMSCl under ambient conditions.

Full text of DOI:10.1002/adsc.201301023

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DOI: 10.1002/adsc.201301023
General Methods for Synthesis of N-Methyliminodiacetic Acid
Boronates from Unstable ortho-Phenolboronic Acids
Su-Jin Ahn,a Chun-Young Lee,a and Cheol-Hong Cheona,*
a
Department of Chemistry, Korea University, Anam-ro, Seongbuk-gu, Seoul 136701, Republic of Korea
Fax : (+82)-2-3290-3121; phone: (+82)-2-3290-3147; e-mail: cheon@korea.ac.kr
Received: November 15, 2013; Revised: February 6, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201301023.
Abstract: A range of N-methyliminodiacetic acid
(MIDA) boronates of commercially available but
unstable ortho-phenolboronic acid derivatives can
be readily prepared through simple condensation
between the corresponding phenolboronic acids and
MIDA in the presence of molecular sieves. The re-
sulting MIDA boronates are bench-top stable and
display a remarkable stability even in DMSO solu-
tion at high temperature (>1208C) compared with
their parent boronic acids. Moreover, the utility of
the resulting MIDA boronate was successfully dem-
onstrated in a cross-coupling reaction using the
slow-release protocol to afford the cross-coupled
product in much better yield compared with its
parent boronic acid counterpart. In addition, an al-
ternative, but more efficient, synthetic route for dif-
ficult-to-access ortho-phenol MIDA boronates has
been developed through the MIDA boronate for-
mation of methoxymethyl (MOM) protected ortho-
phenolboronic acid, followed by deprotection of the
MOM group with TMSCl under ambient condi-
tions.
on the stability of areneboronic acids, there have
been few studies on the actual stability of these bor-
onic acids, and some commercially available arene-
boronic acids are not stable. For instance, we have re-
cently found that ortho- and para-phenolboronic acids
are unstable and rapidly undergo a metal-free thermal
protodeboronation[4] although many of them are cur-
rently commercially available.[5]
Herein we would like to report a general solution
for the preparation of MIDA boronates from unstable
ortho-phenolboronic acids through simple dehydra-
tion between the boronic acids and MIDA. The re-
sulting MIDA boronates are compatible with column
chromatography, bench-top stable, and display a re-
markable stability even in DMSO solution at high
temperature (>1208C) as compared with their parent
boronic acids. Furthermore, the resulting MIDA
boronate was successfully applied to cross-coupling
reactions using the slow-release protocol developed
by the Burke group[9a] to yield the cross-coupled prod-
uct in much better yield as compared with its parent
boronic acid counterpart. In addition, we further de-
veloped a more efficient method for the preparation
of these MIDA boronates via a two-step sequence:
MIDA boronate formation of MOM-protected ortho-
phenolboronic acids, followed by deprotection of the
MOM protecting group.
Keywords: methoxymethyl (MOM) group; N-meth-
yliminodiacetic acid (MIDA); MIDA boronates;
ortho-phenolboronic acids; trimethylsilyl (TMS)
chloride
Recently, the Burke group has developed MIDA
boronates as bench-top stable and efficient surro-
gates[6–9] for a wide range of boronic acids including
highly unstable heteroaromatic boronic acids, such as
Boronic acids are considered an attractive class of 2-pyridylboronic acid derivatives.[9] Consequently, the
synthetic intermediates for the synthesis of a wide utility of MIDA boronates as surrogates for boronic
range of natural products, pharmaceuticals, and mate- acids has been widened recently,[10–13] and many
rials due to their unique reactivity, ready availability, MIDA boronates, including those from unstable bor-
and low toxicity.[1] Although some of the boronic onic acid derivatives, are currently commercially
acids, in particular heteroaromatic boronic acids, are available.[14] We were rather curious about why the
known to be unstable,[2] many areneboronic acids are MIDA boronate from an ortho-phenolboronic acid is
generally believed to be stable and, thus, more than not commercially available, whereas the MIDA
9000 areneboronic acid derivatives are currently com- boronates from meta- and para-phenolboronic acids[15]
mercially available.[3] In contrast to the general belief are commercially available.
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Scheme 1. Formation of MIDA boronate and competing protodeboronation of 1a. Under the conditions developed by the
Burke group,[7] protodeboronation exclusively took place (k2 @k1) to yield 4a rather than 2a.
Based on our recent studies on the protodeborona- as developed by Burke and co-workers using a Dean–
tion of ortho- and para-phenolboronic acids,[4] we en- Stark condenser to remove water.[7] As expected, 2a
visaged that the unavailability of the ortho-phenol was not observed under these conditions; instead
MIDA boronate might be ascribed to competing ther- phenol 4a was obtained in quantitative yield via pro-
mal protodeboronation of ortho-phenolboronic acids todeboronation (Table 1, entry 1). With this result in
under the conditions for the preparation of MIDA hand, we expected that the formation of MIDA
boronates[7] developed by Burke and co-workers boronate 2a could be achieved if the competing pro-
(Scheme 1).
todeboronation were suppressed or proceeded in
In order to test this hypothesis, we first attempted a negligible rate. During our studies for the protode-
to prepare MIDA boronate 2a from ortho-phenolbor- boronation of ortho- and para-phenolboronic acids,
onic acid 1a and MIDA 3 with azeotropic distillation the protodeboronation was found to proceed signifi-
cantly more slowly in the absence of water.[4] Thus,
we carried out the reaction in the presence of molecu-
lar sieves. Delightfully, 2a was obtained in 60% yield
Table 1. Optimization of the reaction conditions.
along with the protodeboronation product 4a
(entry 2). Since the solvent was also found to strongly
influence the protodeboronation of ortho-phenolbor-
onic acids,[4] we investigated the effect of solvents on
the synthesis of 2a (entries 3–7). The choice of solvent
was also turned out to have a strong influence on the
formation of MIDA boronate 2a. Among the solvents
tested, DMF and propionitrile provided the best
result; 2a was obtained in quantitative yield in both
solvents without any protodeboronation (entries 4
and 7). Since the reaction proceeded much faster in
DMF than in propionitrile, we chose DMF as the sol-
vent of choice for further investigation. Next, the
effect of the amount of MIDA 3 on the formation of
2a was investigated (entry 8). The amount of 3 could
be lowered to 1.5 equivalents and the desired product
was obtained in quantitative yield albeit after
a longer reaction time. However, since the unreacted
MIDA 3 was easily recovered by a simple recrystalli-
zation in acetone,[16] we decided to keep using the
3.0 equivalents of 3 to accelerate the formation of
MIDA boronate 2a.
Entry
Solvent
Temp.
[oC]
Time
[h]
Yield[a] [%]
(2a:4a)
AHCTUNGTRENNUNG
1[b]
2
3
4
5
DMSO/toluene
DMSO/toluene
DMSO
DMF
toluene
1,4-dioxane
EtCN
DMF
120
120
120
120
110
110
110
120
12
6
6
0:100
60:40
64:36
1
100:0 (92)[c]
12
18
6
N.R.[d]
6
50:50
7
100:0 (93)[c]
100:0
8[e]
18
Under these optimized conditions, we investigated
the scope of ortho-phenolboronic acids 1 for the for-
mation of MIDA boronates 2 (Table 2). Since many
ortho-phenolboronic acid derivatives are commercial-
ly available,[5] we purchased some of these boronic
acids from commercial suppliers. It turned out that
the purity of starting boronic acids 1 was critical for
[a]
Yields were determined by 1H NMR analysis of the
crude mixtures.
Reaction was performed in the absence of molecular
sieves.
The value in parenthesis is the isolated yield of 2a.
N.R. means no reaction.
1.5 equivalents of 3 were used.
[b]
[c]
[d]
[e]
2
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Methods for Synthesis of N-Methyliminodiacetic Acid Boronates
Table 2. Substrate scope.
Entry
1
2
Yield[a] [%]
X
Y
Scheme 2. Comparison of the thermal stabilities of 1a and
2a.
1
2
3
4
H
H
H
F
OMe
H
H
F
Cl
H
H
H
2a
2b
2c
2d
2e
2f
92
95
94
96
96
98
5
6[b]
[b]
Isolated yields.
para-Phenolboronic acid was used.
[b]
the success of the preparation of MIDA boronates 2.
When the commercially available boronic acids were
directly used without further purification in the
MIDA boronate synthesis, the resulting MIDA
boronates 2 were obtained in moderate yields along
with some other side-products.[17] However, when the
boronic acids were purified by recrystallization in
water and then subjected to the optimized conditions,
the corresponding MIDA boronates 2 were obtained
Scheme 3. Comparison of the efficiencies of 1a and 2a in the
Suzuki coupling reaction.
Although we have developed a new protocol for
in excellent yields. The substituents on the phenyl the synthesis of MIDA boronates 2 from problematic
ring system had very little effect on the yield of ortho-phenolboronic acids 1 by simple condensation
MIDA boronate formation (entries 1–5). In addition, of 1 with MIDA 3 in the presence of molecular sieves,
this protocol could be extended to the MIDA boro- we often encountered rather serious problems, in par-
nate formation for para-phenolboronic acid and the ticular with boronic acids 1 that are highly prone to
corresponding MIDA boronate was obtained in excel- undergo protodeboronation. Although boronic acid
lent yield (entry 6).[15]
1a was used right after purification, the isolated yield
With these MIDA boronates in hand, we compared of 2a fluctuated from moderate to high due to the dif-
the stability of the resulting MIDA boronate with that ficulty in removal of MIDA boronate from boric acid
of its parent boronic acid. In contrast to ortho-phenol- from 2a.[18] In addition, since ortho-phenolboronic
boronic acids 1, the resulting MIDA boronates 2 are acid derivatives are used as one of the most important
bench-top stable. In addition, they displayed remark- synthetic intermediates in organic synthesis, particu-
able stability even in solution state at high tempera- larly, the synthesis of the polyphenol-based natural
ture, compared with their parent boronic acids; bor- products,[19] we needed to develop a more general and
onic acid 1a completely underwent protodeboronation reliable protocol to access these important intermedi-
at 1208C in DMSO within a couple of hours, while ates. Thus, we attempted to develop an alternative
the corresponding MIDA boronate 2a remained method for the preparation of MIDA boronates 2
intact for more than 2 weeks under the same condi- from ortho-phenolboronic acids 1.
tions (Scheme 2).
During our studies on the protodeboronation, it
The advantage of the resulting MIDA boronates was found that only ortho- and para-phenolboronic
was further demonstrated in cross-coupling reactions acids can undergo protodeboronation. For example,
(Scheme 3). When the MIDA boronate 2a was ap- when the phenolic hydroxy group was protected, no
plied to the cross-coupling reaction using the slow-re- protodeboronation took place at all.[4] Thus, we envis-
lease protocol developed by Burke and co-workers,[9a] aged that the ortho-phenol MIDA boronates 2 could
the desired coupling product 5 was obtained in better be prepared via the formation of MIDA boronates 2-
yield than from the reaction with the boronic acid P of protected phenolboronic acids 1-P, followed by
counterpart.
the deprotection of the phenolic hydroxy group.
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Table 3. Alternative synthetic method for MIDA boronate 2a.
Entry
P
Yield[a] [%] of 2a-P
Conditions
Yield[a] [%]of 2a
1
2
3
4
5
6
7
8
Me
Me
Me
Bn
TBS
MOM
MOM
MOM
73
73
73
BBr3, CH2Cl2, r.t., 24 h
BBr3, CH2Cl2, reflux, 24 h
TMSI, ClCH2CH2Cl, reflux, 24 h
N.R.[b]
N.R.[b]
N.R.[b]
93
Pd
–
N
N.R.[b]
N.R.[b]
96
–
HCl (4 N), H2O/THF, 408C, 24 h
TMSCl+NaI, CH3CN, r.t., 1 h
TMSCl, CH3CN, r.t., 12 h
decomposition
70
95
96
96
[a]
Isolated yields.
N.R. means no reaction.
[b]
In order to demonstrate this idea, we first explored ever, it turned out that the removal of the MOM
various protecting groups of 1a (Table 3). When group from the MIDA boronate was not trivial. After
a methyl-protected ortho-phenolboronic acid, 1a-Me, several attempts to deprotect the MOM group, we fi-
was used, the corresponding MIDA boronate from nally found the optimal reaction conditions. When 2a-
1a-Me could be easily prepared in high yield. Rather MOM was treated with TMSI in situ generated from
unexpectedly, we were not able to deprotect the TMSCl and NaI, the desired product was obtained in
methyl group in 2a-Me under several reported condi- 70% yield in 1 h (entry 7). More efficiently, when a-
tions[20] (entries 1–3). Then, we tested other protecting MOM was treated with 6 equivalents of TMSCl under
groups, which could be deprotected under neutral ambient conditions, the MOM group could be easily
conditions.[21] Although a benzyl-protected ortho-phe- removed the desired product 2a was obtained in very
nolboronic acid 1a-Bn afforded the corresponding high yield (entry 8).[22]
MIDA boronate 2a-Bn in excellent yield under the
In conclusion, we have developed a new method
standard conditions, deprotection of the benzyl group for the preparation of bench-top stable MIDA
from 2a-Bn also turned out to be challenging boronates of unstable ortho-phenolboronic acids
(entry 4). Since the deprotection of the phenolic hy- through the simple condensation between boronic
droxy group did not seem to be easy, we attempted to acids 1 and MIDA 3 in the presence of molecular
use a TBS group as a protecting group for 1a. When sieves. Various ortho-phenolboronic acids provided
a TBS-protected phenolboronic acid, 1a-TBS, was the desired MIDA boronates in excellent yields. Al-
used, rather surprisingly, the corresponding MIDA ternatively, we have also developed a more efficient
boronate 2a-TBS was not formed despite several at- method to access ortho-phenol MIDA boronates via
tempts to introduce the MIDA group onto the boron- a two-step sequence: the formation of MIDA boro-
ic acid moiety (entry 5).
nate of an MOM-protected ortho-phenolboronic acid
These results suggested that steric bulk of the and the subsequent deprotection of the MOM group
MIDA moiety might play a critical role in the forma- with TMSCl under ambient conditions. The resulting
tion of the MIDA boronate from a protected phenol- MIDA boronates displayed remarkable stability as
boronic acid and/or deprotection of the resulting compared with the parent boronic acids even in wet
MIDA boronate. Thus, we attempted to utilize other DMSO solution at high temperature. Furthermore,
protecting groups in which the reacting site for the the resulting MIDA boronate was successfully applied
deprotection is farther located from the MIDA to slow-release cross-coupling reactions to yield the
boronate moiety, and chose a methoxymethyl (MOM) cross-coupled product in much better yield compared
group as a protecting group of 1a. The corresponding with that from its parent boronic acid counterpart.
MIDA boronate, 2a-MOM, was readily prepared Further application of MIDA boronates is currently
from this boronic acid under the aforementioned con- underway in our laboratory.
ditions. With this MIDA boronate in hand, we at-
tempted to find suitable reaction conditions for the
deprotection of the MOM group affording 2a. How-
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Methods for Synthesis of N-Methyliminodiacetic Acid Boronates
[3] Based on a SciFinder substructure search using phenyl-
Experimental Section
boronic acid, more than 9000 phenylboronic acid deriv-
atives are commercially available as of November 2013.
[4] C.-Y. Lee, S.-J. Ahn, C.-H. Cheon, J. Org. Chem. 2013,
78, 12154–12160.
[5] The numbers of commercially available ortho- and
para-phenolboronic acid derivatives are 62 and 37, re-
spectively, as of November 2013.
[6] For a seminal report on MIDA boronates, see: E. P.
Gillis, M. D. Burke, J. Am. Chem. Soc. 2007, 129, 6716–
6717.
Direct Synthesis of 2 from 1 via Dehydration
To a round-bottom flask equipped with a stir bar were
added a purified boronic acid 1 (1.0 mmol, 1.0 equiv.),
MIDA 3 (0.44 g, 3.0 mmol, 3.0 equiv.), molecular sieves
(0.36 g), and DMF (10.0 mL). The reaction mixture was
heated at 1208C under an argon atmosphere and monitored
by TLC. On the complete consumption of 1, the reaction
mixture was cooled to room temperature and concentrated
under reduced pressure. The crude mixture was re-dissolved
in acetone and undissolved solid was collected by filtration
to recover unreacted MIDA 3. The filtrate was purified by
flash column chromatography on silica gel using acetone as
an eluent to afford a white solid. The solid obtained was dis-
solved in a minimum of acetone to which Et2O was slowly
added to promote crystallization. MIDA boronate 2 was col-
lected by filtration.
[7] For a review on MIDA boronates, see: E. P. Gillis,
M. D. Burke, Aldrichimica Acta 2009, 42, 17–27.
[8] For recent examples of applications of MIDA boro-
nates, see: a) S. Fujii, S. Y. Chang, M. D. Burke, Angew.
Chem. 2011, 123, 8008–8010; Angew. Chem. Int. Ed.
2011, 50, 7862–7864; b) E. M. Woerly, J. R. Struble, N.
Palyam, S. P. OꢁHara, M. D. Burke, Tetrahedron 2011,
67, 4333–4343; c) S. J. Lee, T. M. Anderson, M. D.
Burke, Angew. Chem. 2010, 122, 9044–9047; Angew.
Chem. Int. Ed. 2010, 49, 8860–8863; d) E. M. Woerly,
A. H. Cherney, E. K. Davis, M. D. Burke, J. Am. Chem.
Soc. 2010, 132, 6941–6943; e) J. R. Struble, S. J. Lee,
M. D. Burke, Tetrahedron 2010, 66, 4710–4718; f) S. G.
Ballmer, E. P. Gillis, M. D. Burke, Org. Syn. 2009, 86,
344–359; g) B. E. Uno, E. P. Gillis, M. D. Burke, Tetra-
hedron 2009, 65, 3130–3138; h) E. P. Gillis, M. D.
Burke, J. Am. Chem. Soc. 2008, 130, 14084–14085;
i) S. J. Lee, K. C. Gray, J. S. Paek, M. D. Burke, J. Am.
Chem. Soc. 2008, 130, 466–468.
[9] a) G. R. Dick, E. M. Woerly, M. D. Burke, Angew.
Chem. 2012, 124, 2721–2726; Angew. Chem. Int. Ed.
2012, 51, 2667–2672; b) G. R. Dick, D. M. Knapp, E. P.
Gillis, M. D. Burke, Org. Lett. 2010, 12, 2314–2317;
c) D. M. Knapp, E. P. Gillis, M. D. Burke, J. Am. Chem.
Soc. 2009, 131, 6961–6963.
[10] a) Z. He, A. Zajdlik, J. D. St. Denis, N. Assem, A. K.
Yudin, J. Am. Chem. Soc. 2012, 134, 9926–9929; b) Z.
He, A. K. Yudin, J. Am. Chem. Soc. 2011, 133, 13770–
13773.
Synthesis of 2 from an MOM-Protected ortho-
Phenolboronic Acid via a Two-Step Sequence
2-Methoxymethoxyphenylboronic acid 1a-MOM (0.18 g,
1.0 mmol, 1.0 equiv.), MIDA 3 (0.44 g, 3.0 mmol, 3.0 equiv.),
and molecular sieves (0.36 g) were dissolved in DMF
(10 mL). The reaction mixture was heated to 1208C and
monitored by TLC. On the complete consumption of 1a-
MOM, the reaction mixture was cooled to room tempera-
ture and concentrated under reduced pressure. The crude
mixture was re-dissolved in acetone and unreacted MIDA
was removed by filtration. The filtrate was concentrated and
re-dissolved in MeCN (8.0 mL). To the above solution was
added TMSCl (6.0 mmol; 6.0 equiv.) in CH2Cl2 at room tem-
perature. On complete consumption of the MOM-protected
phenol MIDA boronate, the mixture was evaporated to
afford the crude mixture. The crude mixture obtained was
dissolved in a minimum of acetone to which Et2O was
slowly added to promote crystallization. Product 2a was col-
lected by filtration and obtained as a white crystalline solid.
[11] a) J. E. Grob, M. A. Dechantsreiter, R. B. Tichkule,
M. K. Connolly, A. Honda, R. C. Tomlinson, L. G.
Hamann, Org. Lett. 2012, 14, 5578–5581; b) J. E. Grob,
J. Nunez, M. A. Dechantsreiter, L. G. Hamann, J. Org.
Chem. 2011, 76, 10241–10248; c) J. E. Grob, J. Nunez,
M. A. Dechantsreiter, L. G. Hamann, J. Org. Chem.
2011, 76, 4930–4940.
[12] For the use of chiral MIDA boronates in diastereose-
lective synthesis, see: J. Li, M. D. Burke, J. Am. Chem.
Soc. 2011, 133, 13774–13777.
Acknowledgements
This work was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF)
funded by the Ministry of Science, ICT and Future Planning
(NRF-2013R1A1A1008434). C.-H.C. also thanks the Ministry
of Education (NRF20100020209) for financial support from
the NRF fund.
[13] For the use of chiral MIDA boronates in diastereo-
meric resolution to access axially chiral compounds,
see: C.-Y. Lee, C.-H. Cheon, J. Org. Chem. 2013, 78,
7086–7092.
[14] More than 170 MIDA boronates are currently commer-
cially available from Aldrich as of November 2013.
[15] When we started this research, meta-phenol MIDA bor-
onate was already commercially available, while ortho-
and para-phenol MIDA boronates were not commer-
cialized at that time. However, para-phenol MIDA bor-
onate 2f was commercialized by Aldrich very recently.
References
[1] D. G. Hall, in: Boronic Acids: Preparation and Applica-
tions in Organic Synthesis Medicine and Materials, 2nd
edn., Vol. 1, (Ed.: D. G. Hall), Wiley-VCH, Weinheim,
2005, pp 1–133.
[2] E. Tyrell, P. Brookes, Synthesis 2003, 469–483.
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[16] MIDA 3 is not soluble in acetone, while the resulting
phenol MIDA boronates 2 are soluble in acetone.
Using the difference in solubility between 3 and 2, un-
reacted 3 could be easily recovered from the reaction
mixture by simple filtration.
[17] The major by-product was the MIDA boronate from
boric acid, which was one of the products of protode-
boronation of 1.
[18] MIDA boronates 2 from boronic acids 1 and that from
boric acid have similar solubility and polarity, which
makes them very difficult to separate by conventional
purification methods.
[19] For a review on the synthesis of axially chiral natural
products, see: G. Bringmann, T. Gulder, T. A. Gulder,
M. Breuning, Chem. Rev. 2011, 111, 563–639.
[20] T. W. Greene, P. G. M. Wuts, in: Protective Groups in
Organic Synthesis, 3rd edn., Wiley-VCH, Weinheim,
1998, pp 250–257.
[21] Since MIDA boronates are known to be easily convert-
ed into the parent boronic acids under basic conditions,
we decided not to use protecting groups, which could
be removed under basic conditions, see ref.[7]
[22] a) J. R. Falck, K. K. Reddy, S. Chandrasekhar, Tetrahe-
dron Lett. 1997, 38, 5245–5248; b) J. W. Huffman, X.
Zhang, M.-J. Wu, H. H. Joyner, W. T. Pennington, J.
Org. Chem. 1991, 56, 1481–1489.
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General Methods for Synthesis of N-Methyliminodiacetic
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