SYnthesis of N-(tert-butoxycarbonyl)-β-Iodoalanine methyl ester: A Useful building block in the synthesis of nonnatural α-amino acids via palladium catalyzed cross coupling reactions: (L-Alanine, N-[(1,1-dimethylethoxy)carbonyl]-3-iodo-, methyl ester)

Full text of DOI:10.15227/orgsyn.081.0077

DOI:10.15227/orgsyn.081.0077
Organic Syntheses, Vol. 81, p. 77-88 (2005); Coll. Vol. 11, p. 384-392 (2009).
SYNTHESIS OF N-(tert-BUTOXYCARBONYL)-ꢀ-IODOALANINE
METHYL ESTER: A USEFUL BUILDING BLOCK IN THE
SYNTHESIS OF NONNATURAL ꢁ-AMINO ACIDS VIA
PALLADIUM CATALYZED CROSS COUPLING REACTIONS
(L-Alanine, N-[(1,1-dimethylethoxy)carbonyl]-3-iodo-, methyl ester)
BocHN
BocHN
BocHN
CO Me
BocHN
CO Me
2
2
TsCl, Et N
3
A.
B.
4-DMAP (cat)
Me NHCl (cat)
OTs
3
OH
CH Cl , 0°C
2
2
2
3
1
BocHN
CO Me
CO Me
2
2
NaI, acetone
OTs
I
2
CO Me
2
1) Zn+
BocHN
CO Me
2
C.
CO Me
2
2)
I
I
4
3
CO Me
2
Pd dba , P(o-Tol)
2
3
3
DMF, 60°C
1
Submitted by Richard F. W. Jackson and Manuel Perez-Gonzalez.
Checked by Rick L. Danheiser and Aimee L. Crombie.
1
. Procedure
A.
N-(tert-Butoxycarbonyl)-O-(p-toluenesulfonyl)-L-serine methyl
ester (2). A one-necked, 500-mL, round-bottomed flask equipped with a
rubber septum and magnetic stirbar was charged with 26.1 g (119 mmol) of
N-(tert-butoxycarbonyl)-L-serine methyl ester (1) (Note 1) and 200 mL of
CH Cl (Note 2). The solution is cooled in an ice bath at 0 °C while 0.700 g
2
2
(6.0 mmol) of 4-dimethylaminopyridine (4-DMAP), 1.1 g (12 mmol) of
77

Me NHCl (Note 3), and 22.7 g (119 mmol) of freshly recrystallized p-
3
toluenesulfonyl chloride (TsCl) (Note 4) are added. The septum is replaced
with a dropping funnel charged with 17 mL (119 mmol) of triethylamine
(
Et N) in 50 ml of CH Cl which is added dropwise to the reaction mixture
3
2
2
at 0 °C over 40 min (Note 5). The resulting slurry is stirred at 0 °C for 2 h
and then poured into a mixture of 100 mL of ice, 100 mL of water, and 50
mL of 2M HCl solution. The aqueous layer is extracted with 100 mL of
CH Cl , and the combined organic layers are washed with two 60-mL
2
2
portions of brine, dried over magnesium sulfate, and concentrated by rotary
evaporation to yield 59.4 g of a light yellow solid. This product may contain
ca. 15% of starting material and TsCl that can be efficiently removed by
crystallization according to the following procedure. The solid is dissolved
in 140 mL of hot diethyl ether, filtered, and the filtrate is allowed to cool to
room temperature and then to 0 °C. Once crystallization begins (Note 6), a
total of 250 mL of petroleum ether is added in five portions over 2 h and
then crystallization is allowed to proceed at ꢀ20 °C overnight. The crystals
are collected by suction filtration on a Büchner funnel and air-dried to give
28.3-30.8 g (64-69%) of 2 as a white solid (Note 7).
B. N-(tert-Butoxycarbonyl)-ꢁ-iodoalanine methyl ester (3). A one-
necked, 250-mL, round-bottomed flask equipped with a rubber septum and
magnetic stirbar is charged with 27.8 g (74.0 mmol) of N-(tert-
butoxycarbonyl)-O-(p-toluenesulfonyl)-L-serine methyl ester (2) and 160
mL of acetone (Note 8). The solution is stirred at room temperature and
1
3.4 g (89.0 mmol) of NaI (Note 9) is added in one portion. The reaction
mixture is stirred in the dark for 3 days, after which an additional 3.3 g (22
mmol) of NaI is added and stirring is continued for an additional day (Note
1
0). The reaction mixture is then suction filtered through a sintered glass
funnel and the filtrate is collected in a one-necked, 500-mL, round-bottomed
flask. The solid is washed with acetone until it is colorless. The solid is
discarded and the filtrate is concentrated by rotary evaporation under
reduced pressure (Note 11). The residual yellow oil is partitioned between
1
50 mL of diethyl ether and 60 mL of 1M sodium thiosulfate (Na S O )
2
2
3
solution. The organic layer is separated and washed with 40 mL of 1M
Na S O 50 mL of brine, dried over magnesium sulfate, filtered, and
2
2
3
concentrated by rotary evaporation (Note 11) to afford 23.2 g of a colorless
oil that solidifies on standing at 0 °C. The solid is dissolved in 30 mL of hot
78

(40 °C) petroleum ether (bp 35-45 °C), cooled to room temperature and then
to 0 °C. Once a precipitate appears (Note 6), the mixture is cooled at –20 °C
for 1 h and the white solid is collected on a Büchner funnel and washed with
cold petroleum ether to yield 19.4-20.0 g (80-82%) of N-(tert-
butoxycarbonyl)-ꢀ-iodoalanine methyl ester 3 as white to pale yellow
crystals (Note 12).
C.
N-(tert-Butoxycarbonyl)-ꢀ-[4-(methoxycarbonyl)phenyl]alanine
methyl ester (4). A three-necked, 100-mL, round-bottomed flask equipped
with an argon inlet adapter, reflux condenser, rubber septum, and magnetic
stirbar (Note 13) is charged with 2.7 g (42 mmol) of zinc dust and 0.039 g
(
0.15 mmol) of I . The flask is evacuated to 0.03 mm and heated with a heat
2
gun for 10 min, flushed three times with argon, and then allowed to cool to
room temperature. Dimethylformamide (1 mL) (Note 14) is added via
syringe, and then a solution of 10.8 g (33 mmol) of iodide 3 in 14 mL of
DMF is added dropwise via syringe to the well-stirred suspension of zinc
dust. The reaction mixture is stirred for 30 min at 0 °C to produce a solution
of the zinc reagent and a suspension of excess zinc dust. The ice bath is
removed and 7.9 g (30 mmol) of methyl 4-iodobenzoate (Note 15), 0.137 g
(0.15 mmol) of tris(dibenzylideneacetone)dipalladium (0), and 0.183 g (0.6
mmol) of tri-o-tolylphosphine are added. The reaction mixture is then
stirred at 60 °C for 5 h. The resulting mixture is poured into a conical flask
containing 300 mL of water. An additional 100 mL of 10% citric acid
solution is added in order to break the black emulsion. The aqueous layer is
extracted with two 150-mL portions of diethyl ether, and the combined
organic layers are washed with two 100-mL portions of water and 100 mL of
brine. At this point, the organic extracts are decanted from a black solid
[
consisting of palladium and zinc(0), together with a bright white solid;
Note 16)], dried over magnesium sulfate, filtered, and concentrated by
(
rotary evaporation to yield 9.1 g of a pale yellow solid. This material is
purified by column chromatography (Note 17). The product is charged on a
column of 200 g of silica gel (Sorbent 60A, 32-63 ꢀm) and eluted with 1 L
of 20% EtOAc-hexane. At that point, fraction collection (25-mL fractions)
is begun, and elution is continued with 500 mL of 25% EtOAc-hexane and
then 200 mL of 30% EtOAc-hexane. The desired product is collected in
fractions 13-59 which are concentrated by rotary evaporation to yield 3.5-
3.9 g (35-39%) of 4 as a white solid (Note18).
79

2
. Notes
1
.
The checkers purchased N-(tert-butoxycarbonyl)-L-serine
methyl ester from Aldrich Chemical Company, Inc. The submitters
prepared this compound, a thick amber oil, according to the procedure
described in Dondoni, A.; Perrone, D. Org. Synth. Coll. Vol. X, 2004, 320.
2
.
The checkers purified dichloromethane by pressure filtration
through activated alumina.
The checkers purchased 4-DMAP and Me N·HCl from Aldrich
3
.
3
Chemical Company, Inc. Et N was purchased from Alfa Aesar Chemical
3
Company and was distilled from CaH . The submitters obtained 4-DMAP
2
and Et N from Lancaster and Me N·HCl from Aldrich Chemical Company,
3
3
Inc.
4
.
TsCl was obtained from Aldrich Chemical Company, Inc. and
purified by recrystallization according to the following procedure. p-
Toluenesulfonyl chloride (85 g) is dissolved in 150 mL of hot CHCl and
3
200 mL of petroleum ether (room temperature) is added in one portion to the
clear, colorless solution. The resulting cloudy solution is clarified by
addition of ca. 5 g of charcoal, stirred for 1 min, and filtered on a Büchner
funnel. The filtrate is concentrated to ca. 1/5th of its original volume by
rotary evaporation, and the solid which appears is collected by filtration and
dried under reduced pressure (25 °C, 0.03 mm) to afford 68 g of TsCl as
bright white crystals.
5
.
Triethylamine addition must be carried out slowly to avoid
base-promoted elimination of p-toluenesulfonate in the final product.
It may be necessary to scratch the flask in order to start
crystallization.
The product exhibits the following properties: mp 74-76 °C,
6
.
7
.
7
a
20
D
7b
lit. 74-75 °C; [ꢀ] + 3.0 (methanol, c 2.0), lit. +4.6 (methanol, c 2); Rf
-
1
0
1
2
1
.24 (petroleum ether/EtOAc 3:1); IR (CH Cl ) cm : 3384, 2979, 1753,
2
2
1
714, 1511, 1367, 1191, 1177; H NMR (500 MHz, CDCl ) ꢁ: 1.43 (s, 9 H),
3
.46 (s, 3 H), 3.71 (s, 3 H), 4.29 (dd, J = 10.1, 3.1 Hz, 1 H), 4.40 (dd, J =
0.1, 3.1 Hz, 1 H), 4.50-4.53 (m, 1 H), 5.30 (d, J = 7.9 Hz, NH), 7.37 (app d,
1
3
J = 7.9 Hz, 2 H), 7.77 (app d, J = 8.2 Hz, 2 H); C NMR (125 MHz, CDCl )
3
ꢁ
: 21.9, 28.4 (3 C), 53.1 (2 C), 69.7, 80.7, 128.2 (2 C), 130.1 (2 C), 132.5,
80

+
+ t
1
45.4, 155.1, 169.2; MS (EI) m/z 314 (M -CO Me, 20%), 300 [(M -O Bu),
2
+
8
%], 258 [(M -BocNH ), 13%], 215 (11%), 155 (TolSO , 43%), 57 (100%);
2
2
+
HRMS (EI) m/z: [M – CO Me] calcd for C H NO S, 314.1057; found,
2
14 20
5
314.1059.
8
.
A.C.S. Reagent grade acetone (99.5%) was purchased from
Aldrich Chemical Company, Inc.
The checkers purchased sodium iodide from Mallinckrodt
Chemical Co. and dried it under vacuum (0.03 mm) at 100 °C for 2 days.
0. The reaction can be monitored by TLC: elution with 3:1
petroleum ether/ethyl acetate, R = 0.24 (O-tosylserine), R = 0.60
9
.
1
f
f
(
iodoalanine).
1. Due to the unstable nature of the iodide, the solution should be
cooled in an ice-water bath at 0 °C during concentration.
2. Iodoalanine derivative 3 is also available from Aldrich
Chemical Company, Inc. Compound 3 exhibits the following spectroscopic
1
1
6
b
20
and physical properties: mp 45-47 °C, lit.
mp = 51 °C; [ꢀ] ꢁ3.7
D
6
b
20
(
MeOH), c 3.0, lit. [ꢀ] = ꢁ4.0 (c 3 methanol); R 0.60 (petroleum
f
D
-1
ether/AcOEt 3:1); IR (CH Cl ) cm : 1163, 1259, 1422, 1714, 1748, 2986,
2
2
1
3
054, 3424; H NMR (500 MHz, CDCl ) ꢂ: 1.47 (s, 9 H), 3.55-3.67 (m, 2
3
H), 3.81 (s, 3 H), 4.53-4.54 (m, 1 H), 5.36 (d, J = 6.4 Hz, 1 H); C NMR (125
MHz, CDCl ꢂ: 8.6, 29.0 (3 C), 53.7, 54.4, 81.2, 155.5, 170.8,; MS (EI) m/z
3
+
+
2
70 (M -CO Me 25%), 214 [(M -Boc), 8%], 57 (100%); HRMS (ESI) m/z:
2
+
[
M + Na] calcd for C H INO , 352.0016; found, 352.0021; Anal. Calcd
9
16
4
for C H INO : C, 32.8; H 4.9; N, 4.3. Found: C, 33.2; H 4.8; N, 4.1.
9
16
4
1
3. The submitters used a two-necked, round-bottomed flask
equipped with a magnetic stirbar, three-way stopcock connected to vacuum
and a N source, and a solid addition tube. The addition tube was charged
2
with methyl 4-iodobenzoate, tris(dibenzylideneacetone)dipalladium(0), and
tri-o-tolylphosphine. After the zinc reagent was formed and the ice bath was
removed, the solids contained in the addition tube were added in one portion
by inverting the tube.
1
4. DMF was distilled from CaH and stored over activated 4Å
2
molecular sieves.
81

1
5. Methyl 4-iodobenzoate was purchased from Avocado Chemical
Co. Zinc dust (< 10 microns, 95% purity) was purchased from Aldrich
Chemical Ccompany, Inc. The checkers purchased Pd dba and P(o-Tol)
2
3
3
from Strem Chemicals, Inc. and l from Mallinckrodt. The submitters
2
purchased Pd dba and P(o-Tol) from Aldrich Chemical Company, Inc.
2
3
3
1
6. This solid was identified as dimethyl biphenyl-4,4’-
1
dicarboxylate: H NMR (200MHz, CDCl ) ꢀ: 3.96 (s, 6H), 7.67-7.72 (BB’,
3
4
H), 8.10-8.16 (AA’, 4H); mp 219-220 °C, (lit. mp 214-217 °C: Catalogue
handbook of Fine Chemicals. Aldrich 1999-2000).
7. The submitters purified the product by the following procedure.
1
The residual pale yellow solid is dissolved in 50 ml of diethyl ether and the
remaining solid is filtered off (Note 16). The filtrate is concentrated to a
volume of ca. 25 mL, and the solution is allowed to crystallize at 0 °C. Once
crystallization begins, 50 mL of petroleum ether is added in two portions
over 10 h, and then crystallization is allowed to proceed overnight at 0 °C.
The white solid is collected by filtration and washed with a mixture of 3:1
petroleum ether-diethyl ether to afford 3.8 g of 4. Chromatographic
purification of the mother liquor (5.5 x 18 cm of DSH silica gel 40-63 mm,
elution with 1 L of petroleum ether/ethyl acetate 4:1 followed by 1.5 L of
3
:1 petroleum ether-ethyl acetate) gives 2.5 g of 4 as a pale yellow solid. All
the material is combined and recrystallized from diethyl ether/petrol as
above to yield 5.2 g (47%) of 4 in two crops.
1
8. The enantiomeric purity of compound 4 was higher than 99.5%
as determined by HPLC (2-cm Supelco Si precolumn, 250 x 4.6 mm
Chiralpak AS, 10% isopropanol in heptane, 1mL/min, t = 14.5 min). The D
r
enantiomer (t = 11.5 min) was not detected. Alternatively, the Boc
r
protecting group of compound 4 (0.100 g) was removed by treatment with a
solution prepared by addition of 100 ꢀL of AcCl to 1.5 mL of methanol.
Mosher’s amides were formed using i-Pr NEt (1.1 equiv), EDCI (1.1 equiv),
2
BtOH (1.1 equiv) and (R) or (S)-ꢁ-methoxy-ꢁ-(trifluoromethyl)phenylacetic
1
acid (1.5 equiv), and H NMR (500 MHz) analysis of both amides showed
ee > 98%. Compound 4 exhibits the
following spectroscopic and analytical
2
0
-1
1
.0); IR (CH Cl ) cm :
properties: mp 82-83 °C; [ꢁ] = ꢂ5.0 (acetone, c
2
2
D
3
367, 2979, 2954, 1720, 1613, 1512, 1282, 1167; 1H NMR (500 MHz,
CDCl ) ꢀ: 1.42 (s, 9 H), 3.10 (dd, J = 13.7, 6.4 Hz, 1 H), 3.20 (dd, J = 13.7,
3
82

5
.8 Hz, 1 H), 3.91 (s, 3 H), 3.72 (s, 3 H), 4.61-4.63 (m, 1 H), 5.00 (d, J = 7.9
1
3
Hz, NH), 7.21 (app d, J = 7.9 Hz, 2 H), 7.98 (app d, J = 8.5 Hz, 2 H); C
NMR (125 MHz, CDCl ) ꢀ: 29.0 (3 C), 39.1, 52.8, 53.1, 54.9, 80.8, 129.6,
3
+
1
0
8
30.1 (2 C), 130.5 (2 C), 142.2, 155.7, 167.6, 172.7; MS (EI) m/z 337 (M ,
+
+
t
+
.3%), 306 [(M ꢁOMe), 7%], 264 [(M ꢁO Bu), 4%], 220 [(M ꢁBocNH ),
2
+
3%], 150 (79%), 57 (100%); HRMS (ESI) m/z: [M + Na] calcd for
C H NO 360.1418; found, 360.1407; Anal. Calcd for C H NO : C,
1
7
23
6
17 23
6
6
0.51; H, 6.88; N, 4.15. Found: C, 60.3; H, 6.6; N, 4.0.
Waste Disposal Information
All toxic materials were disposed of in accordance with "Prudent
Practices in the Laboratory"; National Academy Press; Washington, DC,
995.
1
3
. Discussion
The development of synthetic equivalents for the alanine ꢂ-anion is an
important target for the synthesis of ꢃ-amino acids. A useful solution was
provided by the discovery that organozinc reagents could be prepared from
the iodoalanine derivative (3) by insertion of activated zinc into the carbon-
2
iodine bond. The resulting organometallic reagent could then be coupled
with carbon electrophiles in the presence of a suitable palladium catalyst.
Furthermore, treatment of the organozinc reagent with copper cyanide gave
the organocuprate, which could then couple directly with reactive
3
electrophiles.
The iodoalanine derivative is available in both enantiomeric forms
and this method offers an extremely simple route to large numbers of non-
4
natural amino acids. Therefore a reliable and practical method for the
synthesis of fully protected iodoalanine 3 in a multigram scale is highly
desirable.
83

Although the tosylation reaction of fully protected serine has already
5
been described, we have found that extended reaction times are required
when the reaction is carried out on 100-200 mmol scale, taking from 3 to 5
days to go to completion. As a result of longer reaction times, the amount of
by-products is increased making the purification step more difficult.
Recently Tanabe and co-workers have found that several alcohols
were smoothly and efficiently tosylated using tosyl chloride/ triethylamine
6
and a catalytic amount of trimethylamine hydrochloride as reagents.
Compared with the traditional method using pyridine as solvent, this
procedure has the merit of much higher reaction rates, and it avoids the side
reaction in which the desired tosylate is converted into the corresponding
chloride.
84

Yielda
Entry
Electrophile
Catalyst
T(°C), t
Product
ꢀ
O N
2
Pd (dba) 1%
NHBoc
2
3
rt, 2 h
72%b
1
P(oTol) 4%
3
O N
2
CO Me
2
ꢀ
Br
Pd (dba) 1.2%
NHBoc
2
3
47%b
40 °C, 5.5h
2
3
P (oTol) 5%
3
Br
CO Me
2
NHBoc
Cl Pd(PPh )
2
3 2
52%c
5
0 °C, 5h
5%
Br
Br
N
Br
Br
Br
N
N
CO
2
Me
NHBoc
CO
NHBoc
CO Me
Cl Pd(PPh )
2
3 2
64%d
50 °C, 5.5h
4
5
2
%
N
N
Br
Br
Me
2
Cl Pd(PPh )
2
3 2
34%e
4
0 °C, 6h
5%
H N
H N
N
2
2
2
a) Isolated yield. b) 5 mmol scale. c) 10 mmol scale. d) 7 mmol scale. e) 2 mmol scale.
85

Stirring a mixture of tosylate and NaI in acetone at room temperature
for four days produced the iodoalanine derivative 3 via a pseudo-Finkenstein
reaction. Although this reaction has been reported to proceed in shorter
7
reaction times when carried out at reflux, in our hands, an increase in the
temperature of the reaction produced significant amounts of by-products and
a poor mass balance. For instance, when the experimental procedure stated
in step B was carried out at reflux of acetone only 4 g of crude material was
recovered. Three water-soluble products account for the rest of the mass
balance, and one of them has been identified as 4-
8
methoxycarbonyloxazolidin-2-one. Better yields can be obtained when the
reaction was carried out at reflux on a smaller scale (2 g of compound 2) and
7
under much more dilute conditions as reported. It is our contention that due
to the instability of the iodoalanine derivative, high temperatures during the
reaction or the work-up promote decomposition of the product via
intramolecular nucleophilic attack by the carbamate moiety. Nevertheless,
compound 3 could be kept in the refrigerator for one year without evidence
of decomposition.
The procedure in Section C is representative of the synthesis of non-
natural ꢀ-amino acids featuring the palladium cross coupling reaction of a ꢁ-
alanine organozinc derivative with aromatic electrophiles. This methodology
has been successfully extended with modifications to both the electrophile
and the catalyst as shown in the Table.
Applications of the zinc reagent derived from iodide 3 continue be
reported, and a recent comprehensive review, which updates reference 4, has
9
been published. A range of other amino acid-derived organozinc reagents
have been prepared (5 and 6 from aspartic acid, and 7 and 8 from glutamic
acid) and been shown to undergo Negishi coupling with aromatic iodides
under similar conditions to those reported in the procedure. In general,
reactions of zinc reagents 5-8 proceed at lower temperatures, and with
significantly higher yields, than the zinc reagent derived from iodide 3. This
is largely due to the greater reactivity of zinc reagents 5-8.
NHBoc
NHBoc
NHBoc
NHBoc
CO Me
ZnI IZn
IZn
2
MeO C
ZnI
MeO C
CO Me
2
2
2
5
6
7
8
86

The method for zinc activation now routinely used for step C involves
addition of the iodine to a rapidly stirred suspension of zinc dust in
dimethylformamide under an atmosphere of nitrogen, followed by stirring at
1
0
room temperature until the iodine decolorizes (typically < 5min).
This
procedure is simpler than the reported method and allows very similar
results to be obtained.
1
2
3
4
5
6
7
. Department of Chemistry, The University of Sheffield, Sheffield, S3
7HF, UK
. Jackson, R. F. W.; Wishart, N.; Wood, A.; James, K.; Wythes, M. J. J.
Org. Chem. 1992, 57, 3397.
. Dunn, M. J.; Jackson, R. F. W.; Pietruszka, J.; Turner, D. J. Org. Chem.
1
995, 60, 2210.
. For a review see: Gair, S.; Jackson, R. F. W. Current Org. Chem. 1998,
, 527.
2
. Hermkens, P. H. H.; Maarseveen, J. H. v.; Ottenheijm, H. C. J.; Kruse, C.
G.; Scheeren, H. W. J. Org. Chem. 1990, 55, 3998.
. Yoshida, Y.; Sakakura, Y.; Aso, N.; Okada, S.; Tanabe, Y. Tetrahedron
1999, 55, 2183.
. a) Stocking, E. M.; Schwarz, J. N.; Senn H.; Salzmann, M.; Silks, L. A.
J. Chem. Soc., Perkin Trans. 1 1997, 2443. b) Bajgrowicz, J. A.; A. El
Hallaoui; Jacquier, R.; Pigiere, Ch.; Viallefont, P. Tetrahedron 1985, 41,
1
833.
. Sibi, M. P.; Rutherford, D.; Sharma, R. J. Chem. Soc., Perkin Trans.1
994, 1675.
8
1
9
. Rilatt, I. Caggiano, L.; Jackson, R.F.W. Synlett 2005, 2701.
0. Huo, S. Org. Lett. 2003, 5, 423.
1
87

Appendix
Chemical Abstracts Nomenclature (Registry Number)
N-(tert-Butoxycarbonyl)-L-serine methyl ester: L-Serine, N-[(1,1-
dimethylethoxy)carbonyl]-, methyl ester; (2766-43-0)
N-(tert-Butoxycarbonyl)-ꢀ-iodoalanine methyl ester: L-Alanine, N-[(1,1-
dimethylethoxy)carbonyl]-3-iodo-, methyl ester; (93267-04-0)
N-(tert-Butoxycarbonyl)-ꢀ-4-(methoxycarbonyl)phenyl]alanine methyl
ester: L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-4-
(
methoxycarbonyl)-, methyl ester; (160168-19-4)
4-Dimethylaminopyridine: 4-Pyridinamine, N,N-dimethyl-; (1122-58-3)
Trimethylamine hydrochloride: Methanamine, N,N-dimethyl-,
hydrochloride; (593-81-7)
p-Toluenesulfonyl chloride: Benzenesulfonyl chloride, 4-methyl-; (98-59-
9
)
Triethylamine: Ethanamine, N,N-diethyl-; (1221-44-8)
Sodium iodide: Sodium iodide (NaI); (7681-82-5)
Sodium thiosulfate: Thiosulfuric acid (H S O ), disodium salt; (7772-98-7)
2
2
3
Methyl 4-iodobenzoate: Benzoic acid, 4-iodo-, methyl ester; (619-44-3)
Tris(dibenzylideneacetone)dipalladium: tris[μ-[(1,2-ꢁ:4,5-ꢁ)-(1E,4E)-1,5-
diphenyl-1,4-
pentadien-3-one]]di-; (51364-51-3)
Tri-o-tolylphosphine: Phosphine, tris(2-methylphenyl)-; (6163-58-2)
Zinc; (7440-66-6)
Iodine; (7553-56-2)
Dimethyl biphenyl-4,4'-dicarboxylate: [1,1'-Biphenyl]-4,4'- dicarboxylic
acid, dimethyl
ester; (792-74-5)
88