A convenient synthesis of 4-trifluoromethyl-(2H)-pyridazin-3-ones from methyl 3,3,3-trifluoropyruvate

Article abstract of DOI:10.1055/s-2005-871926

A convenient two-step synthesis of 4-CF₃-(2H)-pyridazin-3-ones starting from methyl 3,3,3-trifluoropyruvate (MeTFP) and carbonyl compounds has been elaborated. As a result, a set of various 4-CF₃-(2H)-pyridazin- 3-ones was obtained.

Full text of DOI:10.1055/s-2005-871926

LETTER
1907
A Convenient Synthesis of 4-Trifluoromethyl-(2H)-pyridazin-3-ones from
Methyl 3,3,3-Trifluoropyruvate
S
ynthesis of 4-Trif
m
luoromethyl-(2
H
)-p
i
yridaz
tres iy A. Sibgatulin, Dmitriy M. Volochnyuk, Alexandr N. Kostyuk*
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska 5, Kyiv-94, 02094, Ukraine
Fax +380(44)5373253; E-mail: a.kostyuk@enamine.net
Received 28 April 2005
Introduction of fluorine-containing substituents is a very
useful tool for changing physico-chemical properties of
molecules, which are widely used in the search for new
drugs. At the same time there are only a few reported stud-
ies devoted to synthesis of derivatives of trifluoromethyl-
containing pyridazine derivatives.1,3 It should be noted
that the synthesis of 4-trifluoromethyl-(2H)-pyridazin-3-
ones 2 (R¢ = CF3) was accomplished in four steps starting
from commercially unavailable compounds in low overall
yields (Scheme 1). The increasing interest in fluorinated
heterocyclic compounds4 prompted us to develop a
general method for the synthesis of 4-trifluoromethyl
pyridazine derivatives. The general approach to (2H)-
pyridazin-3-ones bearing various substituents at the 4-
position is the reaction of a-hydroxy-g-ketoacids with
hydrazine derivatives (Scheme 1).5 However, this very
convenient approach has never been applied to synthesis
of 4-trifluoromethyl pyridazine derivatives, despite the
fact that derivatives of a-hydroxy-a-CF3-g-ketoacids are
known in the literature.6–8 Synthesis of these compounds
can easily be carried out by reaction of methyl 3,3,3-tri-
fluoropyruvate (MeTFP) with carbonyl compounds or
enamines.
Abstract: A convenient two-step synthesis of 4-CF3-(2H)-py-
ridazin-3-ones starting from methyl 3,3,3-trifluoropyruvate
(MeTFP) and carbonyl compounds has been elaborated. As a result,
a set of various 4-CF3-(2H)-pyridazin-3-ones was obtained. The
scope and limitations of the methodology is defined.
Key words: methyl 3,3,3-trifluoropyruvate, pyridazinones, tri-
fluoromethyl, aldol condensation, cyclocondensation
The pyridazine nucleus is an interesting heterocyclic ring,
which plays the role of a pharmacophore in several classes
of derivatives possessing a variety of pharmacological
properties.1 In the past, great attention has been particular-
ly paid to various (2H)-pyridazin-3-ones due to their
synthetic versatility, well-balanced physico-chemical
properties, and the presence of possible binding sites for
interaction with various receptors. Some derivatives have
become promising drug candidates.2 Therefore, function-
alization and fine-tuning of substituents around the
pyridazine nucleus is an activity of continued interest in
the overall design and development of drugs.
Additionally, (2H)-pyridazin-3-ones are very useful start-
ing materials for synthesis of libraries based on the py-
ridazine scaffold, for example, 3-(alkylamino)pyridazine
derivatives of type 1, potential biologically active com-
pounds.
A wide set of ketones was used by us in the reaction with
MeTFP affording derivatives 7a–j. Optimized conditions
were found to be heating equivalent amounts of ketone
and MeTFP at 100 °C in a pressure tube. Under these con-
ditions in the majority of cases ketones transform into the
corresponding aldols in almost quantitative yields so that
analytically pure products can be prepared by triturating
products with hexane. There are a few exceptions such as
pyridylmethylketones 6e–g, in that cases the reaction mix-
tures underwent extensive resinification and in the case of
acetylpyrrole 6j, which was shown to react at the pyrrole
ring as well.9 In these cases, analytically pure products can
be prepared by silica gel column chromatography using
EtOAc as eluent (Scheme 2, Table 1).
Scheme 1
Scheme 2 Reagents and conditions: i: 1 equiv MeTFP, 100 °C,
1–5 h, neat; ii: 3 equiv NH2NH2·H2O, AcOH, reflux, 1 h.
SYNLETT 2005, No. 12, pp 1907–1911
Advanced online publication: 07.07.2005
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1
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DOI: 10.1055/s-2005-871926; Art ID: D11605ST
© Georg Thieme Verlag Stuttgart · New York

1908
D. A. Sibgatulin et al.
LETTER
The aldols 710–13 react readily with hydrazine in acetic ing additional groups was offered. In the reaction with
acid during one hour affording the targeted 4-trifluoro- hydrazines, additional electrophilic centers participate in
methyl-(2H)-pyridazin-3-ones 8a–k14–17 in high yields the reactions affording cyclocondensation products
(Table 1).
(Scheme 3).
In our previous work7 a convenient method for the synthe-
sis of trifluoromethyl containing aldols of type 7 contain-
Table 1 Yields, Reaction Time and Melting Points of Compounds 7 and 8
Substrates 6
Time
(h)a
Products 7
Yield Mp
Products 8
Yield
(%)b
Mp
(%)b
(°C)c
(°C)c
O
a
1
1
98
61e
95
187–189f
H
N
O
CO2Me
OH
O
N
CH3 CH3
CH3
CF3
CH3
CF3
dF = –86.6 ppm
dF = –67.8 ppm
b
85
91
51
96
111
O
O
H
CO2Me
N
O
N
CH3
OH
CF3
CF3
dF = –77.9 ppm
dF = –66.3 ppm
c
d
e
f
1
2
3
4
58–60g
97
89
82
78
150 (dec)
O
CO2Me
H
N
O
O
N
OH
CF3
CF3
dF = –75.8 ppm
dF = –59.5 ppm
97
51
42
84h
144i
O
O
H
N
CO2Me
OH
O
N
CH3
CF3
CF3
dF = –80.0 ppm
dF = –66.7 ppm
O
67
213
O
H
N
CO2Me
O
N
OH
CH3
CF3
N
N
CF3
N
dF = –80.0 ppm
dF = –66.6 ppm
117
H
198–200
O
O
CO2Me
OH
N
O
N
CH3
CF3
CF3
N
N
N
dF = –66.1 ppm
g
h
1
3
62
85
137
52
85
81
206
180
O
H
O
CO2Me
OH
N
O
N
CH3
CF3
N
CF3
N
N
dF = –77.8 ppm
dF = –66.2 ppm
O
H
N
CO2Me
CH3
O
N
O
OH
O
CF3
O
CF3
dF = –80.2 ppm
O
dF = –66.2 ppm
Synlett 2005, No. 12, 1907–1911 © Thieme Stuttgart · New York

LETTER
Synthesis of 4-Trifluoromethyl-(2H)-pyridazin-3-ones
1909
Table 1 Yields, Reaction Time and Melting Points of Compounds 7 and 8 (continued)
Substrates 6
Time
(h)a
Products 7
Yield Mp
Products 8
Yield
(%)b
Mp
(%)b
(°C)c
(°C)c
i
4
3
5
82
84
86
81
91
204–206
O
H
CO2Me
CH3
N
O
N
S
OH
O
O
CF3
S
CF3
S
dF = –80.1 ppm
dF = –66.1 ppm
j
80d
Oili
134
193
225
H
O
CO2Me
OH
N
O
CH3
N
N
H
CF3
NH
CF3
NH
dF = –80.4 ppm
dF = –65.9 ppm
k
67
H
O
O
CO2Me
OH
N
O
N
CH3
CF3
CF3
O
O
O
dF = –77.8 ppm
dF = –66.2 ppm
a According to 19F NMR spectra of the reaction mixture.
b Isolated yields.
c Melting points are uncorrected.
d Data of 19F NMR spectra of the reaction mixture.
e Lit. 61–63 °C.6a
f Lit. 190–191 °C.3
g Lit. 57–59 °C.6a
h Lit. 85–87°C.6a
i Purity >85%, but can be used for following transformation without purification. Analytically pure products can be prepared by silica gel column
chromatography using EtOAc as eluent (Rf = 0.8); Mp = 99–101 °C.
The course of the reaction depends on the character of Thus, for compound 9a (EWG = CN) reaction with hy-
the electron-withdrawing function in the starting com- drazine leads to the formation of the targeted pyridazin-3-
pounds 9.
one (10).18 In the case of aldol 9b (EWG = COPh), the
reaction proceeds with participation of the additional
carbonyl group affording pyrazole 11.19 In a case of
compound 9c (EWG = CO2Et) the reaction runs non-
regioselectively, affording the mixture of targeted py-
ridazin-3-one (12) and pyrazolone 13.20
In conclusion, a convenient synthesis of 4-CF3-(2H)-py-
ridazin-3-ones starting from methyl 3,3,3-trifluoropyru-
vate (MeTFP) and carbonyl compounds has been
elaborated. As a result, a set of various 4-CF3-(2H)-py-
ridazin-3-ones was obtained. A wide set of substrates
performed well in the reaction. Nevertheless, some limita-
tions were encountered in the development of this meth-
odology. The presence of additional functional groups
reactive toward hydrazine in the starting CF3-containing
aldols can lead to other products.
Acknowledgment
The authors acknowledge A.V. Mazepa (Bogatsky Physico-Chemi-
cal Institute, National Academy of Sciences of Ukraine, Depart-
ment of Molecular Structure), A.Y. Petin and V.V. Polovinko
(Enamine LTD) for spectroscopic measurements.
Scheme 3 Reagents and conditions: i: 3 equiv NH2NH2·H2O,
AcOH, reflux, 1–3 h.
Synlett 2005, No. 12, 1907–1911 © Thieme Stuttgart · New York

1910
D. A. Sibgatulin et al.
LETTER
Compound 7i: 13C NMR (100 MHz, CDCl3): d = 41.0, 54.2,
75.2 (CCF3, 2JCF = 29.5 Hz), 122.1 (CF3, 1JCF = 285.3 Hz),
128.4, 133.1, 135.1, 142.7, 169.2, 187.4.
References
(1) Conteras, J.-M.; Rival, Y. M.; Chayer, S.; Bourguignon, J.-
J.; Wermuth, C. G. J. Med. Chem. 1999, 42, 730.
(2) (a) Yoshinori, K.; Tomoyuki, K.; Hiromichi, S.; Hideo, Y.;
Takahiro, K.; Shunji, T.; Kyoko, Y.; Junko, T.; Seiichi, S.
U.S. Pat. Appl. Publ. US 2004002497, 2004; Chem. Abstr.
2004, 140, 77155. (b) Matyus, P.; Maes, B. U. W.; Riedl, Z.;
Hajos, G.; Lemiere, G. L. F.; Tapolcsanyi, P.; Monsieurs, K.;
Elias, O.; Dommisse, R. A.; Krajsovszky, G. Synlett 2004,
1123; and references therein.
(13) Typical MS data (MX-1321 instrument) of aldols 7.
Compound 7f: MS (EI, 70 eV): m/z (%) = 277 (4) [M+], 218
(26) [M+ – CO2Me], 106 (100) [3-pyridyl – CO+], 78 (40) [3-
pyridyl+], 51 (17).
Compound 7g: MS (EI, 70 eV): m/z (%) = 277 (5) [M+], 218
(27) [M+ – CO2Me], 106 (100) [4-pyridyl – CO+], 78 (42)
[4-pyridyl+], 51 (21).
Compound 7i: MS (EI, 70 eV): m/z (%) = 282 (4) [M+], 223
(15) [M+ – CO2Me], 111 (100) [2-thienyl – CO+], 39 (16).
(14) Typical Procedure for Preparation of (2H)-Pyridazine-3-
ones 8.
(3) (a) Brule, C.; Bouillon, J.-P.; Nicolai, E.; Portella, C.
Synthesis 2003, 436. (b) Kamitori, Y.; Sekiyama, T.
Heterocycles 2004, 63, 707.
(4) (a) Fluorine in Bioorganic Chemistry; Filler, R.; Kobayasi,
Y.; Yagupolskii, L. M., Eds.; Elsevier: Amsterdam, 1993.
(b) Hudlicky, M. Chemistry of Organic Fluorine
Compounds; Ellis Horwood: Chichester, 1992. (c) Kukhar,
V. P.; Soloshonok, V. A. Fluorine-Containing Amino Acids,
Synthesis and Properties; Wiley: New York, 1995.
(5) (a) Wermuth, C. G.; Schlewer, G.; Bourguignon, J.-J.;
Maghioros, G.; Bouchet, M.-J.; Moire, C.; Kan, J.-P.;
Worms, P.; Biziere, K. J. Med. Chem. 1989, 32, 528.
(b) Coates, W. J.; McKillop, A. Synthesis 1992, 334.
(c) Baraldi, P. G.; Bigoni, A.; Cacciari, B.; Caldari, C.;
Manfredini, S.; Spalluto, G. Synthesis 1994, 1158.
(d) Yoshida, N.; Awano, K.; Kobayashi, T.; Fujimori, K.
Synthesis 2004, 1554.
(6) (a) Golubiev, A. S.; Galakhov, M. V.; Kolomiets, A. F.;
Fokin, A. V. Izv. Akad. Nauk SSSR, Ser. Khim. 1989, 9,
2127. (b) Palecec, J.; Paleta, O. Synthesis 2004, 521.
(7) Volochnyuk, D. M.; Kostyuk, A. N.; Sibgatulin, D. A.;
Petrenko, A. E. Synthesis 2004, 2545.
(8) Paleta, O.; Palesek, J.; Dolensky, B. J. Fluorine Chem. 2001,
111, 175.
(9) Zhuang, W.; Gathergood, N.; Hazell, R. G.; Jorgensen, K. A.
J. Org. Chem. 2001, 66, 1009.
To a solution of aldol 7 (1 equiv) in HOAc (5 mL)
NH2NH2·H2O (3 equiv) was added. The reaction mixture
was refluxed for 1 h. After cooling the solvent was
evaporated in vacuum and the residue was triturated with
H2O affording 8.
(15) Typical 1H NMR data (Varian Mercury-300 spectrometer)
of 4-trifluoromethyl-(2H)-pyridazine-3-ones 8.
Compound 8f: 1H NMR (300 MHz, DMSO-d6): d = 7.54 (1
H, t, 3JHH = 7.2 Hz, CH), 8.31 (1 H, d, 3JHH = 7.2 Hz, CH),
8.51 (1 H, s, CH), 8.66 (1 H, d, 3JHH = 3.6 Hz, CH), 9.12 (1
H, s, CH), 13.97 (1 H, br s, NH).
Compound 8g: 1H NMR (300 MHz, DMSO-d6): d = 8.52 (2
H, d, 3JHH = 6.3 Hz, CH), 9.10 (1 H, s, CH), 9.29 (2 H, d,
3JHH = 6.3 Hz, CH).
Compound 8i: 1H NMR (300 MHz, DMSO-d6): d = 7.18 (1
H, s, CH), 7.69 (1 H, s, CH), 7.91 (1 H, s, CH), 8.47 (1 H, s,
CH), 13.73 (1 H, s, NH).
(16) Typical 13C NMR data (Varian Mercury-400 spectrometer)
of 4-trifluoromethyl-(2H)-pyridazine-3-ones 8.
Compound 8f: 13C NMR (100 MHz, DMSO-d6): d = 121.6
(CF3, 1JCF = 271.8 Hz), 123.8, 127.6 (CCF3, 2JCF = 31.9 Hz),
129.7, 130.4 (CCCF3, 3JCF = 5.0 Hz), 133.6, 141.6, 147.1,
150.3, 156.1.
Compound 8g: 13C NMR (100 MHz, DMSO-d6): d = 119.9,
121.5 (CF3, 1JCF = 270.9 Hz), 127.6 (CCF3, 2JCF = 31.6 Hz),
129.9 (CCCF3, 3JCF = 4.9 Hz), 140.9, 141.2, 150.3, 156.3,
172.0.
(10) Typical Procedure for Preparation of Compounds 7a–k.
A neat mixture of ketone 6 (1 equiv) and MeTFP (1 equiv)
in a pressure tube was heated at 100 °C 1–5 h (reaction
mixture was monitored by 19F NMR). After cooling the tube
was opened (Caution! Excessive pressure inside!) and the
residue was triturated with n-hexane yielding targeted
compound 7.
Compound 8i: 13C NMR (100 MHz, DMSO-d6): d = 121.3
(CF3, 1JCF = 271.4 Hz), 127.8, 127.9 (CCF3, 2JCF = 31.2 Hz),
128.4, 128.9, 129.5 (CCCF3, 3JCF = 4.9 Hz), 138.3, 140.3,
156.0.
(11) Typical 1H NMR data (Varian Mercury-300 spectrometer)
of aldols 7.
(17) Typical MS data (MX-1321 instrument) of 4-
trifluoromethyl-(2H)-pyridazine-3-ones 8.
Compound 7f: 1H NMR (300 MHz, CDCl3): d = 3.59 and
3.71 (2 H, AB-syst., 2JHH = 18.0 Hz, CH2), 3.83 (3 H, s,
OCH3), 4.18 (1 H, br s, OH), 7.48 (1 H, dd, 3JHH = 7.8 Hz,
3JHH = 4.8 Hz, CH), 8.13 (1 H, dt, 3JHH = 7.8 Hz, 4JHH = 2.5
Hz, CH), 8.72 (1 H, dd, 3JHH = 4.8 Hz, 4JHH = 2.5 Hz, CH),
9.07 (1 H, d, 4JHH = 2.5 Hz, CH).
Compound 8f: MS (EI, 70 eV): m/z (%) = 242 (9) [M + 1],
241 (100) [M+], 184 (37).
Compound 8g: MS (EI, 70 eV): m/z (%) = 242 (10) [M + 1],
241 (100) [M+], 184 (24).
Compound 8i: MS (EI, 70 eV): m/z (%) = 247 (9) [M + 1],
Compound 7g: 1H NMR (300 MHz, DMSO-d6): d = 3.77 (3
H, s, OCH3), 3.83 (2 H, s, CH2), 7.05, (1 H, s, OH), 7.87 (2
H, d, 3JHH = 6.0 Hz, CH), 8.20 (2 H, d, 3JHH = 6.0 Hz, CH).
Compound 7i: 1H NMR (300 MHz, CDCl3): d = 3.64 and
3.70 (2 H, AB-syst., 2JHH = 17.1 Hz, CH2), 3.93 (3 H, s,
OCH3), 4.24 (1 H, br s, OH), 7.17 (1 H, t, 3JHH = 4.8 Hz,
CH), 7.72 (1 H, d, 3JHH = 4.8 Hz, CH), 7.76 (1 H, d,
3JHH = 4.8 Hz, CH).
246 (100) [M+], 189 (54).
(18) Procedure for Preparation of 1,6-Dihydro-6-oxo-5-
(trifluoromethyl)-3-pyridazineacetonitrile (10).
To a solution of aldol 9a (1 g, 4.2 mmol) in HOAc (10 mL)
NH2NH2·H2O (0.63 g, 12.6 mmol) was added. The reaction
mixture was refluxed for 3 h (reaction mixture was
monitored by 19F NMR). After cooling the solvent was
evaporated in vacuum and the residue was triturated with
H2O and extracted with Et2O (10 mL). The Et2O was
evaporated in vacuum affording 10 (0.68 mg, 81%). Mp 175
°C. 1H NMR (300 MHz, DMSO-d6): d = 4.15 (2 H, s, CH2),
7.93 (1 H, s, CH), 13.8 (1 H, br s, NH). 13C NMR (100 MHz,
DMSO-d6): d = 23.1, 117.1, 121.4 (CF3, 1JCF = 270.8 Hz),
127.8 (CCF3, 2JCF = 31.2 Hz), 132.8, 139.1, 156.5. MS (EI,
70 eV): m/z (%) = 204 (100) [M+], 148 (15), 120 (39), 106
(14), 75 (19).
(12) Typical 13C NMR data (Varian Mercury-400 spectrometer)
of aldols 7.
Compound 7f: 13C NMR (100 MHz, CDCl3): d = 41.0, 54.2,
74.9 (CCF3, 2JCF = 32.9 Hz), 123.1 (CF3, 1JCF = 285.1 Hz),
123.8, 128.3, 131.2, 135.5, 149.4, 154.1, 169.1, 193.6.
Compound 7g: 13C NMR (100 MHz, DMSO-d6): d = 42.1,
53.2, 73.2 (CCF3, 2JCF = 28.2 Hz), 121.3, 123.7 (CF3,
1JCF = 285.7 Hz), 141.8, 151.0, 168.5, 195.2.
Synlett 2005, No. 12, 1907–1911 © Thieme Stuttgart · New York

LETTER
Synthesis of 4-Trifluoromethyl-(2H)-pyridazin-3-ones
1911
(19) Procedure for Preparation of Methyl a-Hydroxy-5-
phenyl-a-(trifluoromethyl)-1H-pyrazole-3-propanoate
(11).
mixture was refluxed for 1 h (reaction was monitored by 19
F
NMR). After cooling the solvent was evaporated in vacuum
and the residue was triturated with Et2O. The solvent was
evaporated and the residue was dissolved in CH2Cl2 (10
mL). The insoluble precipitate was filtered affording 13
(0.43 g, 48%). The mother liquid was evaporated and the
residue was triturated with hexane giving 12 (0.41 g, 47%).
Compound 12: mp 87 °C. 1H NMR (300 MHz, CDCl3): d =
1.3 (3 H, t, 3JHH = 7.2 Hz, CH3), 3.75 (2 H, s, CH2), 7.71 (1
H, s, CH), 10.02 (1 H, br s, NH). 13C NMR (100 MHz,
DMSO-d6): d = 14.4, 20.9, 39.5, 53.6, 61.3, 120.1 (CF3,
1JCF = 272.9 Hz), 127.3 (CCF3, 2JCF = 31.4 Hz), 133.9,
141.8, 156.5, 168.4, 170.0. MS (EI, 70 eV): m/z (%) = 250
(35) [M+], 178 (86) [M+ – CO2Et], 158 (40), 120 (20), 101
(49), 97 (33), 75 (20), 74 (43), 69 (24) [CF3], 51 (25), 43
(100).
To a solution of aldol 9b (1 g, 3.1 mmol) in HOAc (10 mL)
NH2NH2·H2O (0.47g, 9.3 mmol) was added. The reaction
mixture was refluxed for 1 h (reaction mixture was
monitored by 19F NMR). After cooling the solvent was
evaporated in vacuum and the residue was triturated with
H2O affording 11 (0.83 mg, 84%). Mp 98 °C. 1H NMR (300
MHz, DMSO-d6): d = 3.11 and 3.33 (2 H, AB-syst.,
2JHH = 14.1 Hz, CH2), 3.76 (3 H, s, OCH3), 6.46 (1 H, s, CH),
7.04 (1 H, br s, OH), 7.32–7.41 (3 H, m, CH), 7.72 (2 H, d,
3JHH = 6.3 Hz, CH), 12.94 (1 H, br s, NH). 13C NMR (100
MHz, DMSO-d6): d = 31.2 (br, Dn1/2 ca. 30 Hz), 53.7, 78.1
(CCF3, 2JCF = 27.7 Hz), 102.9, 124.6 (CF3, 1JCF = 288.0 Hz),
125.4, 128.1, 129.3, 132.0 (br, Dn1/2 ca. 65 Hz), 141.2 (br,
Dn1/2 ca. 300 Hz), 146.6 (br, Dn1/2 ca. 270 Hz), 168.6. MS
(EI, 70 eV): m/z (%) = 314 (38) [M+], 255 (40) [M+ –
CO2Me], 157 (100) [M+ – MeTFP].
Compound 13: mp 196 °C 1H NMR (300 MHz, DMSO-d6):
d = 2.94 and 3.16 (2 H, AB-syst., 2JHH = 14.4 Hz, CH2), 3.73
(3 H, s, OCH3), 5.24 (1 H, s, CH), 7.0 (1 H, br s, OH), 10.6
(1 H, br s, NH). 13C NMR (100 MHz, DMSO-d6): d = 30.8,
53.6, 77.8 (CCF3, 2JCF = 27.5 Hz), 89.8, 124.4 (CF3,
(20) Procedure for Preparation of Ethyl 1,6-Dihydro-6-oxo-5-
(trifluoromethyl)-3-pyridazineacetate (12) and Methyl
a,5-Dihydroxy-a-(trifluoromethyl)-1H-pyrazole-3-
propanoate (13).
J
CF = 285.6 Hz), 137.3, 160.5, 168.4. MS (EI, 70 eV):
m/z (%) = 254 (10) [M+], 195 (10) [M+ – CO2Me], 98 (100)
To a solution of aldol 9c (1 g, 3.5 mmol) in HOAc (10 mL)
NH2NH2·H2O (0.53 g, 10.5 mmol) was added. The reaction
[M+ – MeTFP].
Synlett 2005, No. 12, 1907–1911 © Thieme Stuttgart · New York