Green chemical synthesis of 2-benzenesulfonyl-pyridine and related derivatives

Article abstract of DOI:10.1021/op700060e

A practical synthesis of 2-benzenesulfonylpyridine, 1, is described which is a key starting material for the manufacture of an investigational new drug candidate at Eli Lilly and Company. An optimized green chemical process was developed which features a novel tandem S_NAr/oxidation under mild conditions to produce the target sulfone, 1, in 86% yield and>99% purity. In addition, this novel, environmentally friendly methodology was found to be general for the synthesis of substituted aromatic pyridyl sulfides and sulfones.

Full text of DOI:10.1021/op700060e

Organic Process Research & Development 2007, 11, 913–917
Technical Notes
Green Chemical Synthesis of 2-Benzenesulfonyl-pyridine and Related Derivatives
William G. Trankle and Michael E. Kopach*
Eli Lilly and Company, Chemical Product Research and DeVelopment, Indianapolis, Indiana 46285, U.S.A.
Abstract:
A practical synthesis of 2-benzenesulfonylpyridine, 1, is described
which is a key starting material for the manufacture of an
investigational new drug candidate at Eli Lilly and Company. An
optimized green chemical process was developed which features
a novel tandem SNAr/oxidation under mild conditions to produce
the target sulfone, 1, in 86% yield and>99% purity. In addition,
this novel, environmentally friendly methodology was found to be
general for the synthesis of substituted aromatic pyridyl sulfides
and sulfones.
Figure 1. Approaches to 2-benzenethiopyridine, 2.
narrow range of substrates. Yet, it was anticipated that a
scalable, environmentally friendly method of aryl sulfide
synthesis could be developed to produce to the target 2-ben-
zenethiopyridine, 2, and related thiopyridines.
Although many methods are known for oxidizing sulfides
to sulfones, very few are practical on a multi-kilogram scale.
In addition, many methodologies exhibit poor functional group
tolerance3 or generate large quantities of hazardous waste.4 By
far, the most common oxidant cited in the chemical literature
is hydrogen peroxide,5 but known safety hazards exist because
of the potential release of oxygen, and recently an incident has
been reported where vapor ignition occurred in a reactor.6 An
attractive alternative to the aforementioned routes for the
synthesis of sulfones is use of sodium hyopochlorite, which is
inexpensive andrelatively non-toxic and which would eliminate
much of the waste-stream issues. Herein we report development
of a high-yielding, mild, green chemical tandem SNAr/oxidation
sequence to produce 1 and related sulfones.
Introduction
A recent program at Eli Lilly and Company required the
synthesis of multi-kilogram quantities of key starting material
2-benzenesulfonylpyridine, 1. In order to meet the aggressive
clinical timeline, rapid development of a safe, robust, and
scalable synthesis of 1 was of high priority. One-pot conditions
have recently been described in the patent literature to produce
2-benzene sulfonyl pyridine derivatives including the target
compound 1.1 Although the reported yields (85%) and purity
(98%) are high for this synthetic approach, this methodology
requires the use of stoichiometric benzenesulfonyl cyanide,
which is not commercially available and is extremely hazardous.
In addition, an excess of crotonaldehyde is employed, which is
also a highly toxic reagent. A practical alternative to the
aforementioned methodology that we envisioned for the syn-
thesis of 1 was direct oxidation of 2-phenylthiopyridine, 2.
Methodologies for preparing functionalized pyridine derivatives
are well known, and there are many natural products and
pharmaceutical drug candidates that contain substituted py-
ridines. However, functionalization of the pyridine ring often
requires long reaction times, use of a transition metal catalyst,
or microwave irradiation to produce thioethers such as 2.2 In
addition, these synthetic methodologies frequently require
cumbersome workup conditions and operate for a relatively
Results and Discussion
2-Benzenethiopyridine, 2, was initially prepared by modi-
fication of a known literature preparation that utilized an SNAr
reaction (Figure 1).7 Although this procedure was effective and
produced thiopyridine 2 in ∼90% crude yield, the synthesis
(3) (a) Brown, D. J.; Ford, P. W. J. Chem. Soc. C 1969, 2720. (b) Carey,
F. A.; Dailey, O.D.; Hernandez, O.; Tucker, J. R. J. Org. Chem. 1976,
41, 3975. (c) Kahne, D.; Walker, S.; Cheng, Y.; Van Engen, D. J. Am.
Chem. Soc. 1989, 111, 6881. (d) Trost, B. M.; Curran, D. P.
Tetrahedron Lett. 1981, 22, 1287.
(4) (a) Scalone, M.; Waldmeier, P. Org. Process Res. DeV. 2003, 7, 418.
(b) Webb, K. S. Tetrahedron Lett. 1994, 35, 3457. (c) Yang, D.; Yip,
Y. C.; Jiao, G. S.; Wong, M. K. J. Org. Chem. 1998, 63, 8952. (d)
Brougham, P.; Cooper, M. S.; Cummersome, D. A.; Heaney, H.;
Thompson, N. Synthesis 1987, 1015. (e) Foti, C. J.; Fields, J. D.;
Kropp, P. J. Org. Lett. 1999, 1 (6), 903. (f) Chen, M.; Patkar, L. N.;
Lin, C. J. Org. Chem. 2004, 69, 2884.
* To
whom
correspondence
should
be
addressed.
E-mail:
kopach_michael@lilly.com.
(1) Koyakumaru et al. U.S. Patent 2001/0051726 A1, 2001. Kuraray Co.,
Ltd.
(5) (a) Lee, D. G.; Singh, N. Org. Process Res. DeV. 2001, 5, 599. (b)
Kaczorowski, Tetrahedron 2005, 61, 8315. (c) Noyori, R. Tetrahedron
2001, 57, 2469. (d) Najera, C. Tetrahedron Lett. 2002, 43, 3459. (e)
Lipton, M. F.; Mauragis, M. A.; Maloney, M. T.; Velley, M. F.;
Vanderbor, D. W.; Newby, J. J.; Appell, R. B.; Daugs, E. D. Org.
Process Res. DeV. 2003, 7, 385.
(2) (a) Cheng, Y. Tetrahedron 2002, 58, 4931. (b) Herradura, P. S.;
Pendola, K. A.; Guy, R. K. Org. Lett. 2000, 2, 2019. (c) Kwong, F. Y.;
Buchwald, S. L. Org. Lett. 2002, 4, 3517. (d) Li, G. Y.; Zheng, G.;
Noonan, A. F. J. Org. Chem. 2001, 66, 8677. (e) Hickman, R. J. S.;
Christie, B. J.; Guy, R. W.; White, T. J. Aust. J. Chem. 1985, 38,
899. (f) Taniguchi, N.; Onami, T. J. Org. Chem. 2004, 69, 915. (g)
Adapa, R. S.; Alam, M. M.; Ramu, R. E. Chem. Lett. (Jpn.) 2004, 33,
1614.
(6) (a) Wehrum, W. Process Saf. Prog. 1993, 12, 199. (b) Astbury, G. R.
Org. Proc. Res. DeV. 2002, 6, 893.
(7) Mcdonald, J. W.; Le Bleu, R. E.; Quin, L. D.; Bradsher, C. K. J. Org.
Chem. 1961, 26, 4944.
10.1021/op700060e CCC: $37.00
Published on Web 07/28/2007
2007 American Chemical Society
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Since the oxidation step was not compatible with DMSO, the
SNAr would have to be performed in a non-reactive aprotic
solvent such as DMF. To this end, a trial SNAr was carried out
in DMF under the same conditions as employed with DMSO,
and the crude reaction performance appeared comparable. While
addition of 10.8% bleach to an unfiltered reaction mixture of
sulfide 2 eventually consumed 2 fully, a mixture of sulfoxide
and sulfone was produced in a 2:1 ratio, which did not improve
even with added bleach. The obvious next step was to test the
oxidation in the absence of carbonate salts. This was ac-
complished by performing the SNAr in 5 volumes of DMF,
cooling the reaction mixture to 23 °C after SNAr completion,
and then filtering off the waste salts. The filtrate was then treated
with concentrated bleach in portions until the sulfide and
resulting sulfoxide were fully consumed as per HPLC analysis.
To facilitate complete conversion of sulfoxide to sulfone, it was
necessary to heat the oxidation mixture to ∼80 °C and maintain
this temperature during the bleach addition. After completion
of the bleach feed, water was added to increase the total aqueous
content to 18 volumes,11 the mixture was then cooled to 5 °C,
and the resulting slurry was filtered and rinsed with water. These
conditions produced pristine 2-phenylsulfonyl pyridine as a
white crystalline solid in 78% over the two steps on a 10-g
scale (Table 1, entry 1). When this procedure was scaled from
20 to 100 g, the yield of 1 improved to 85% and the results
from multiple runs were consistent (Table 1, entries 2–5).
Despite the successes of the tandem SNAr/oxidation sequence
to produce 1, the amount of concentrated NaOCl required for
complete conversion to sulfone was inconsistent from run to
run and generally required 3–4 equiv. The Chapman–Stevens
oxidation is a well-known method for synthesis of aldehydes
and ketones from primary or secondary alcohols,12 and in this
procedure bleach and acetic acid are combined to produce
hypochlorous acid (vide infra), which serves as the active
oxidizing agent. Most commonly, acetic acid is used as solvent
then bleach is added and the product is obtained via an extractive
workup or precipitation. We reasoned that it might be possible
to extend this procedure to the synthesis of sulfones. In addition,
it was reasoned that the acetic acid may impart additional
solubility for the intermediate sulfoxide and further facilitate
the conversion to sulfone. To assess the impact of acetic acid
on the oxidation of 2 with bleach, a DMF solution of crude 2
prepared from the SNAr was treated with 4 equiv of acetic acid,
and then 2 equiv of 10.8% bleach was added over 45 min while
maintaining the pot contents at <45 °C throughout the bleach
feeds. Under these conditions complete conversion to sulfone
was observed without any detectable sulfoxide intermediate.
In a separate experiment the acetic acid charge was reduced to
1.5 equiv, and under these conditions the product crystallized
at 40–45 °C and was isolated in 92% yield. With these results
Figure 2. Oxidation of 2 with concentrated sodium hypochlorite.
was untenable for multi-kilogram scale production for the
following reasons: (1) 2 equiv of thiophenol used for the
reaction was undesirable because of its stench and acute
toxicity;8 (2) excess triethylamine was used to promote the
reaction; (3) benzene was the workup solvent. In addition, an
unsuccessful alternative we explored was preparation of thi-
opyridine 2 via Queguiner’s thioether Grignard approach (Figure
1).9
The SNAr approach was optimized using 1 equiv of
thiophenol and potassium carbonate at 85 °C in DMSO. After
an extractive workup with methyl-tert-butyl ether as a substitute
for benzene, 2-phenylthiopyridine 2 was produced in 90% yield
and contained only small amounts of 2-BrPy, PhSH, and (PhS)2
impurities. Although issues remained surrounding the large
volumes of solvent used in the workup, the SNAr approach was
sufficient for generating large quantities of 2 for evaluation of
the oxidation step. Conversion of sulfide to the sulfone was
initially successfully accomplished via the use of magnesium
bis(monoperoxyphthalate)-hexahydrate (MMPP) in DMF, which
produced clean sulfone in 65–72% yield. However, 5 min after
charging MMPP, a severe safety hazard resulted in that the
mixture exothermed from ambient temperature to ∼150 °C. In
addition, due to the higher molecular weight and low potency
of commercial MMPP (which is sold as an 80 wt % solid), it
was necessary to use four times as much by weight of MMPP
as starting sulfide, which created a large waste disposal issue
on top of the safety concerns. OXONE was also screened and
resulted in incomplete conversion with similar difficulties with
the waste profile. Sodium hypochlorite was the next oxidant
screened, and rather than 5% household bleach, a concentrated
solution of 10–13 wt % NaOCl was evaluated. It was anticipated
that concentrated bleach would reduce the quantity of aqueous
waste and minimize the risk of sulfoxide precipitation, which
was problematic using OXONE. Addition of 2 equiv of
concentrated hypochlorite to a DMF solution containing sulfide
2 resulted in the complete conversion of starting material to
sulfoxide intermediate.10 The resulting mixture was then heated
to 85 °C, and two additional charges of bleach were added
followed by a short stir time to complete conversion to product.
Water was added to bring the total aqueous content to 12.5
volumes (L/kg starting material), the mixture was cooled to 23
°C, and sulfone 2 was collected via filtration in 85% yield
(Figure 2).
With the individual steps worked out in a rough fashion for
the preparation of 2-benzene sulfonyl pyridine, 1, attention was
directed toward telescoping both steps in order to avoid the
troublesome workup and isolation of 2-benzenethiopyridine, 2.
(11) This was an increase from the 12.5 vol of aqueous used in the original
procedure due to the extra DMF and the much lower salt content in
the bleach oxidation as compared to that with MMPP.
(12) (a) Stevens, R. V.; Chapman, K. T.; Weller, H. N. J. Org. Chem.
1980, 45, 2030. (b) Moehrig, J. R.; Nienhuls, D. M.; Linck, C. F.;
Zoeren, C. V.; Fox, B. B.; Mahaffy, P. G. J. Chem. Educ. 1985, 62,
519. (c) Hendrickson, W. H.; Hendrickson, D. G.; Sakai, A. Tetra-
hedron Lett. 2000, 41, 2759.
(8) Thiophenol has been designated a P-code chemical as per 40CFR261.33
that specifies even unused thiophenol is hazardous waste.
(9) Bonnet, V.; Breton, G.; Marsais, F.; Mongin, F.; Quéguiner, G.;
Trécourt, F. Tetrahedron 2000, 56, 1349.
(10) The temperature of the pot contents was raised from 23–60 °C; while
the exotherm for the Trankopach reaction was sharp, it was addition-
rate controlled, an important safety feature.
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Table 1. Tandem SNAr/oxidation
run
scale (g)a
NaOCl (equiv)b
yield (%)
1
2
3
4
5
10
100
25
3.0
3.6
3.7
2.4
4.0
78
86
84
86
85
20
50
a Amount of 2-BrPy used. b Adjusted for titrated strength.
Table 2. Optimized oxidation/SNAr synthesis of 2-phenylsulfonyl pyridine, 1
entry
SNAr temp (°C)
SNAr time (h)
SNAr conv (%)
bleach strength (w/w %)
isolated 1 (g)
yield (%)
purity (%)a
ab
b
110
110
110
110
85
12
17
16
20
13
100
10.6
8.3
10.8
12.6
10.8
24.7
99.7
85.0
87.3
86.7
86.0
88.5
86.7
99.6
100
99.5
99.8
99.1
99.6
98.2
97.4
98.4
97.7
c
99.0
d
148.6
98.2
ec
av
a Purity determined by HPLC relative to 2-phenylsulfonyl pyridine reference standard. b Reaction run with 0.96 equiv of 2-chloropyridine and spiked with 0.05 equiv of
3-chloropyridine. c 2-Bromopyridine comparator.
in hand we proceeded rapidly to scale up this chemistry, and
all future experiments were run by the combined SNAr/oxidation
approach.
consistent crystallization, the amount of water added to the
workup was adjusted to provide a total aqueous content of 12
vol based on the bleach strength; typically after isolation
approximately 6% of 1 is retained in the filtrate. In all cases
tested, a clean conversion to sulfone was achieved with a
maximum operating temperature of 50 °C. In a typical experi-
ment, the bleach feed was commenced at ambient temperature,
then the mixture was heated to 40 °C, and the exotherm of the
reaction was controlled by adjusting the bleach dosing rate.
With the development of a commercial process for the
syntheses of 1 completed, we now had the occasion to
investigate the generality of the methodology to the synthesis
of selected aryl sulfides and sulfones. The first set of sulfone
syntheses evaluated were regioisomeric or disubstituted sulfones
(Table 3, entries b–f) related to 1 that were potential starting
material based process impurities. The SNAr for the dihalopy-
ridines were more facile than with the parent system 2 as a
result of the favorable electronic influence of the additional
electron-withdrawing group. In cases where bis-sulfones were
possible (Table 3, entries d–f), high selectivity for the mono-
sulfones were achieved. Predictably, electron-withdrawing
groups on the pyridine ring resulted in dramatic acceleration in
the SNAr reaction rates. For example, the SNAr reaction for
pyridine substrates containing nitro groups went to completion
within 1 h at 23 °C, and these systems produced the highest
yielding sulfones (93%) of any evaluated via the standard
conditions (Table 3, entries h and i). Similarly, the pyridine
N-oxides saw a rapid increase in reaction rate in the SNAr (Table
3, entries j and k). However, in these cases the yield of isolated
Despite the absence of literature reports of successful tandem
SNAr/oxidation chemistry for sulfone synthesis via aryl chlorides
without activation, we investigated 2-chloropyridine as a
substrate due to the potential large positive economic impact
on the project.13 As shown in Table 2, the results were
exemplary using 2-chloropyridine; the only modification re-
quired in order to achieve equivalent conversion to the bromide
system was to perform the chemistry at 110 °C rather than
80–90 °C. The standard conditions were rapidly scaled, several
runs were performed on a 100-g scale or greater, and the process
was found to work acceptably with bleach strength ranging from
8 to 13% (Table 2) to produce 1 in 85–88% yield, which
allowed us to give the 2-bromopyridine approach the hard
goodbye. Overall, the purity of isolated 1 was excellent in all
cases, and potential positional isomers present in the 2-chloro-
pyridine feedstocks that were evaluated in the synthesis did not
appear to carry through in any significant amount, which was
an important requirement. For example, an experiment was
performed where the SNAr was run with a slight subcess of
2-chloropyridine (0.96 equiv) while spiked with 5 mol % of
3-chloropyridine (Table 2, entry a). In this case, 100% conver-
sion was observed in the SNAr and only a trace amount of
3-benzenesulfonylpyridine, 3 (0.01%) was detected in the
isolated product, 1, as per HPLC analysis. To provide a
(13) Aldrich Pricing: 2-bromopyridine ) $224/500 g or $70.80/mol;
2-chloropyridine ) $73.30/500 g or $16.60/mol.
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Table 3. Tandem SNAr/oxidation evaluation with alternative pyridine and aromatic substrates (HPLC purity data is reported
for isolated solids)
bleach
sulfone
sulfone
compound
no.
entry
R-pyridine
SNAr time (h) SNAr temp (°C) SNAR conv (%) strength (%) purity (%) yield (%)
a
b
c
d
e
f
g
h
i
j
k
l
m
n
2-chloro
16
48
15
3
110
100–120
85
97
95
100
99
100
100
94
100
100
100
99
10.8
10.8
10.8
8.9
>99
98
87
73
83
85
76
85
82
93
93
66
73
86
75
65
1
3
3-bromo
4-bromo
98
4
2,3-dichloro
60
92
5
2,3-dibromo
1
35
50
110
23
23
40
105
90
110
110
12.0
8.9
97
6
2,6-dichloro
1
17
1
92
7
2-chloro-4-methyl
2-chloro-5-nitro
2-chloro-3-nitro
2-bromo- N-oxide
2-chloro- N-oxide
3-chloro-5-cyano
2-chloro-quinoxaline
2-chloro-quinoline
8.9
95
8
8.9
95
9
0.2
8.9
>99
>99
>99
94
10
11
11
12
13
14
0.5
1
8.3
11.7
11.9
12
1
100
100
100
1
>99
95
1
12
Table 4. Tandem SNAr/oxidation with substituted thiophenols
bleach
strength (%)
sulfone
purity (%)
sulfone
yield (%)
compound
no.
entry
thiophenol
Cl/Br
SNAr time (h)
SNAr temp/conv (%)
a
b
c
d
e
f
H
Cl
Cl
Br
Br
Br
Br
Br
Cl
Cl
Br
16
20
4
110/97
110/96
80/100
80/100
95/97
120/100
115/100
110/98
110/98
110/97
10.8
8.9
>99
>99
>99
95
87
76
91
87
72
75
82
89
61
78
1
15
15
16
17
18
19
20
21
22
3-Cl
3-Cl
3-F
3,5-bis(CF3)
2-Br
4-NO2
4-Me
8.9
20
20
16
20
20
5
11.9
12.0
11.0
11.7
8.0
8.3
12.0
97
98
g
h
i
89
92
4-MeO
2-CF3
94
j
18
95
sulfone, 11 was lower as a result of the increased solubility of
the N-oxide products in the filtrate. The most sluggish perfor-
mance in the SNAr was observed with the 3-bromopyridine
substrate, which required 120 °C and 48 h reaction time and
still did not go to completion (Table 3, entry b).
After completing the screening of substituted pyridines, we
next assessed the generality of the tandem SNAr/oxidation
toward substitution on the thiophenol ring (Table 4). Predictably,
electron-withdrawing substituents on the thiophenol ring re-
tarded the SNAr reaction rate, whereas electron-donating sub-
stituents resulted in a slight increase in reaction rate. In most
cases, high quality sulfones were produced by the standard
conditions.
Another class of compounds evaluated under standard
conditions were 2-chloroquinoxaline and 2-chloroquinoline
(Table 3, entries m and n), and in both cases the SNAr was
efficient. Because of the extreme insolubility of their sulfoxide
intermediates, it was not possible to isolate either of the target
sulfones free of sulfoxide contamination under the standard
processing conditions. However, in both cases the isolated
sulfone/sulfoxide mixtures (containing 15–30% sulfoxide im-
purities) were resubjected to the oxidation reaction conditions
to achieve conversion to product in overall 65% and 75% yield.
Finally, we assessed the compatibility of the tandem SNAr/
oxidation sequence to nitrile functionality (Table 3, entry l) and
the SNAr was facile under the standard conditions without nitrile
oxidative hydrolysis.
Conclusion
An efficient, novel, green chemical synthesis for the produc-
tion of 2-benzene-sulfonyl pyridine, 1, has been demonstated,
and we have shown this methodology to be general for the
synthesis of aryl pyridylsulfones. To our knowledge this is an
unprecedented application of a tandem SNAr/oxidation sequence
to produce sulfones, and this methodology potentially has broad
applicability to the synthesis of this class of compounds.
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Experimental Section
provide 2-benzenesulfonyl pyridine (149 g, 676 mmol) in 86
% yield and>99% purity. 1H NMR (500 MHz, CDCl3) δ 8.66
(d, J ) 5.5 Hz, 1H), 8.19 (d, J ) 7.7 Hz, 1H), 8.05 (m, 2H),
7.92 (ddd, J ) 9.3, 7.7, 1.6 Hz, 1H), 7.60 (m, 1H), 7.54 (m,
2H), 7.44 (m, 1H); IR (KBr) 788, 984, 1124, 1166, 1306, 1424,
1446, 1575, 3085 cm-1; MS (TOF) m/z 220.0439 (220.0427
calcd for C11H10NO2S, MH). Anal. Calcd for C11H9NO2S: C,
60.26; H, 4.14; N, 6.39; S, 14.62. Found: C, 60.40; H, 4.02; N,
6.40; S, 14.76.
General. Unless otherwise noted, stated reagents were
commercially available and used without purification. Solvents
were not distilled prior to use, and NMR data were obtained
using a Varian instrument at 300 or 500 mHz for 1H and 125
Hz for 13C. Products were isolated using polypropylene filters
purchased from U.S. Filter, 100% Polypro; Egg-shell finish 20
µm nominal pore size.
Procedure for Preparation of 2-Benzenesulfonyl-pyridine
(1). A 2-L flask is charged with 2-chloropyridine (75 mL, 790
mmol), thiophenol (90 mL, 852 mmol), and DMF (450 mL).
K2CO3 (134.6 g, 962 mmol) is added, and then the mixture is
heated to 110°C and stirred for 20 h. The mixture is filtered
through polypropylene, the waste cake is rinsed with DMF (195
mL), and then the crude sulfide solution and rinsings are
transferred to a 5-L flask. The oxidation is carried out by
addition of glacial HOAc (57 mL, 995 mmol), heating to 40
°C, and addition of 13 wt % NaOCl solution (850 mL, 1.7 mol)
slowly over 2 h. The conversion of the sulfide to sulfoxide and
sulfone is monitored by HPLC. When the oxidation is complete,
water (530 mL) is added, and the heating is discontinued. The
pH of the mixture is raised to 9 with 20 % (w/v) NaOH solution
(250 mL), and the resulting slurry is cooled to <5 °C. The
mixture is stirred cold for 1.5 h and filtered through polypro-
pylene, and then the wetcake rinsed with water (3 × 200 mL).
The cake is dried in a 55 °C vacuum oven for at least 12 h to
Acknowledgment
We thank Dr. Alfio Borghese and Mr. Luc Antoine for their
contributions to this project at its early stages. We also
acknowledge the contributions of Mr. Steven Bandy and Miss
Amy Hargis who developed an HPLC purity method for
compound 1.
Supporting Information Available
General experimental procedures, synthetic details, 1H and
13C NMR spectra for key compounds shown in Tables 1–4.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Received for review March 11, 2007.
OP700060E
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