Novel 1-trifluoromethyl substituted 1,2-ethylenediamines and their use for the synthesis of fluoroquinolones

Article abstract of DOI:10.1016/S0040-4020(00)00107-1

A common approach to the synthesis of 1-trifluoromethyl-1,2- ethylenediamines was developed. Based on these original building blocks the new derivatives of N-substituted fluoroquinolones bearing the trifluoromethyl group were obtained. Through-space transmitted coupling constants ⁷J(F-F) between the trifluoromethyl group and F-8 were measured in the ¹⁹F NMR spectra of all fluoroquinolones examined and assigned unequivocally by using ¹⁹F{¹⁹F} double resonance technique. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00107-1

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1923–1927
Novel 1-Trifluoromethyl Substituted 1,2-Ethylenediamines and
Their use for the Synthesis of Fluoroquinolones
Alexander Ya. Aizikovich,a Maxim V. Nikonov,a Michael I. Kodess,b Vladislav Yu. Korotayev,a
Valery N. Charushinc and Oleg N. Chupakhinb,
*
aDepartment of Chemistry, Ural State University, Ekaterinburg, 620083, Russia
bInstitute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, 20, S. Kovalevskoy Street,
Ekaterinburg, GSP-147, 620219, Russia
cLaboratory of Organic Chemistry, Ural State Technical University, Ekaterinburg, 620002, Russia
Received 24 September 1999; revised 18 January 2000; accepted 3 February 2000
Abstract—A common approach to the synthesis of 1-trifluoromethyl-1,2-ethylenediamines was developed. Based on these original building
blocks the new derivatives of N-substituted fluoroquinolones bearing the trifluoromethyl group were obtained. Through-space transmitted
coupling constants 7JF–F between the trifluoromethyl group and F-8 were measured in the 19F NMR spectra of all fluoroquinolones examined
and assigned unequivocally by using 19F{19F} double resonance technique. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
hydrochloride (2), and 2-diazo-1,1,1-trifluoro-3-nitro-pro-
pane (3) (Scheme 1).4 These starting materials, which
have become available recently,4 provide access to a variety
of 1-trifluoromethyl substituted 1,2-diaminoethanes bearing
two primary amino groups,4d and their N-acyl, N-alkyl or 1-
cycloalkylimino substituted derivatives.
1,2-Ethylenediamines are known to be widely used for the
synthesis of a variety of nitrogen-containing heterocyclic
compounds of practical importance, such as pyrazines,
piperazines, imidazolines and others.1 Also many deriva-
tives of aliphatic amines bearing a-polyfluoroalkyl sub-
stituent, such as aminoacids, aminoalcohols, etc., were
shown to be of special importance due to profound bio-
logical activities.2 1-Trifluoromethyl substituted 1,2-ethyl-
enediamines, which have hitherto been unknown, gained
our attention as promising building blocks for the synthesis
of new bi- and tri-cyclic derivatives of 6-fluoro-4-oxo-1,4-
dihydroquinoline-3-carboxylic acids, a well-known class of
the broad spectrum antibacterials.3
In the reaction of the N-benzoyl derivative of nitroamine 2
(compound 4) with LiAlH4 in absolute ether, reduction of
the nitro group was accompanied, as expected, by conver-
sion of the amide group as well, thus giving N-benzyl substi-
tuted 1-trifluoromethyl-1,2-diamine 5a in a good yield
(Scheme 2). When reacted with tosyl chloride, compound
4 was converted into the 2-N-tosyl derivative 5b. It is worth
noting that when compound 4 was treated with the 1:1
complex LiAlH4-glycerol, reduction of the nitro group
took place predominantly, yielding N-benzoyl-1-trifluoro-
methyl substituted 1,2-ethylenediamine 6, together with a
minor amount of N-benzyl 1,2-diaminoethane 5a (Scheme
2).
Results and Discussion
In this paper we wish to describe an approach to 1-trifluoro-
methyl-1,2-ethylenediamines based on using as starting
materials 2-amino-1,1,1-trifluoro-3-nitro-2-propene (1), its
Another type of functionalization of 1-trifluoromethyl
Scheme 1.
Keywords: fluoroquinolones; trifluoromethyl group; 1-trifluoromethyl-1,2-ethylenediamines.
* Corresponding author. Tel./fax: ϩ7-34-32-741189; e-mail: chupakhin@ios.uran.ru
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00107-1

1924
A. Ya. Aizikovich et al. / Tetrahedron 56 (2000) 1923–1927
Scheme 2.
substituted 1,2-ethylenediamines is based on substitution of
the diazo group in 2-diazo-1,1,1-trifluoro-3-nitropropane (3)
by cycloalkylimines. It is known that secondary amines are
able to cause displacement of the diazo group in aliphatic
diazo compounds, although these reactions take place only
in the presence of copper, palladium or rhodium complexes,
catalyzing insertion of the generated carbenes into the N–H
bond of secondary amines.5 We have found that 2-diazo-
1,1,1-trifluoro-3-nitropropane (3) can easily be transformed
into 2-cycloalkylimino-1,1,1-trifluoro -3-nitropropanes 7a,b
by action of morpholine and piperidine without the use of
any catalysts (Scheme 3). It has been suggested that a plau-
sible reason for such behavior is that compound 3 is able to
generate carbene species from the corresponding anion
derived from 3 under basic conditions.6 Reduction of the
nitro group in compounds 7a,b with LiAlH4 afforded the
corresponding diamines 8a,b (Scheme 3).
2-(2,3,4,5-tetrafluorobenzoyl)acrylate 97 into new deriva-
tives of fluoroquinolones 11a–d (Scheme 4). Nucleophilic
displacement of the ethoxy group in 9 by amines 5a, 8a,b is
presumed to give the corresponding benzoylacrylates
10b–d followed by simultaneous intramolecular amino-
defluorination reaction leading to quinolones 11b–d
(Scheme 4). The exception is the reaction of the N-benzoyl
compound 6 with ethoxyacrylate 9, which requires the
presence of N-methyl-morpholine in the reaction mixture
in order to convert the intermediate 10a into quinolone 11a.
1H NMR Spectral data for fluoroquinolones 11a–d are
characterized by a considerable difference in chemical shifts
of HA and HB signals which are nonequivalent due to the
presence of the neighboring asymmetric carbon, as well as
HA and HB protons coupled to F8 with coupling constants
5JHF of 2–4 Hz (Table 1).
1-Trifluoromethyl substituted 1,2-diamines 5a,6 and 8a,b
appear to be versatile and useful building blocks, as
illustrated by their conversion by action of ethyl 3-ethoxy-
In the 19F NMR spectra of all fluoroquinolones examined
(Table 2) the long-range coupling constants 7J(F-8, F–CF3)
were observed and assigned unequivocally by using the
Scheme 3.
Scheme 4.

A. Ya. Aizikovich et al. / Tetrahedron 56 (2000) 1923–1927
Table 1. H NMR spectral data for fluoroquinolones 11a–d in DMSO-d6
1925
1
Compound
11a
1H Chemical shifts, d (ppm) and coupling constants (Hz)
HA
HB
HX
H2
H5
Other signals
5.2 m
4.53 m
5.3 m
8.73 s
8.00 ddd
3JH5F6ˆ10.5
9.18 d (NH, Jˆ9.5 Hz)
4JH5F7ˆ8.5 Hz
5JH5F8ˆ2.1 Hz
8.11 ddd
11b
4.78 ddd
3.80 ddd
3.42 m
3.93 m
3.80 m
8.29 s
8.55 s
8.48 s
3.98 and 3.70 (NCH2, 2Jˆ12.9 Hz)
2JABˆ14.7 Hz
3JAXˆ3.1 Hz
5JHBF8ˆ3.1 Hz
4.81 ddd
2JABˆ14.7 Hz
3JBXˆ110 Hz
5JHBF8ˆ2.8 Hz
4.57 ddd
3JH5F6ˆ10.1 Hz
4JH5F7ˆ8.1 Hz
5JH5F8ˆ2.8 Hz
8.01 ddd
11c
1.30 t (3H, Jˆ7.1 Hz) and 4.26 m (2H, OEt), 2.55
2JABˆ14.8 Hz
3JAXˆ2.1 Hz
5JHAF8ˆ2.1 Hz
4.77 ddd
2JABˆ14.8 Hz
3JBXˆ10.7 Hz
5JHBF8ˆ3.7 hz
4.55 ddd
3JH5F6ˆ10.5 Hz
4JH5F7ˆ8.5 Hz
5JH5F8ˆ2.1 Hz
8.01 ddd
and 3.05 (2 NCH2), 3.42 and 3.48 (2 OCH2)
11d
1.28 t (3H, Jˆ6.9 Hz) and 4.25 m (2H, OEt), 2.43
2JABˆ14.8 Hz
3JAXˆ2.2 Hz
5JHAF8ˆ2.2 Hz
2JABˆ14.8 Hz
3JBXˆ11.2 Hz
5JHBF8ˆ3.6 Hz
3JH5F6ˆ10.5 Hz
4JH5F7ˆ8.5 Hz
5JH5F8ˆ2.2 Hz
and 2.98 (2 NCH2), 1.39 m (3 CH2)
double resonance 19F{19F} decoupling technique, whilst the
corresponding 6J(F-8, C–CF3) couplings were not observed
in the 13C NMR spectra (see experimental part). The
presence of 7JF–F coupling and the absence of 6JC–F coupling
support the hypothesis of a through-space pathway for the
transmission of the spin information between the aromatic
fluorine atom C8–F and the trifluoromethyl group which is
due to the geometrical proximity of the interacting nuclei.8
through-space interaction between aromatic fluorine atom
C8–F and the trifluoromethyl group.
Experimental
General procedures
Solvents were purified according to standard procedures. 1H
NMR spectra were measured in solution of DMSO-d6 and
CDCl3 on a Bruker WM-250 (250 MHz) and a Tesla BS-
587 A (80 MHz) spectrometers, 19F NMR spectra—on a
Tesla BS-587 A (75.3 MHz) spectrometer. All signals are
given in ppm (d) with tetramethylsilane as an internal
standard for 1H and hexafluorobenzene for 19F. Double reso-
nance experiments 1H{19F} and 19F{19F} were performed on
a Tesla BS-587A supplied with a specially designed
decoupler operating on 19F frequency.9
Conclusion
In conclusion we point out that a new effective method for
obtaining of 1-trifluoromethyl-1,2-ethylenediamines from
2-amino-1,1,1-trifluoro-3-nitropropanes can be useful for
the synthesis of a variety of biologically active compounds
or intermediates, as illustrated in this paper by the synthesis
of a number of new fluoroquinolones. The presence of the
long-range coupling 7J(F-8, F–CF3) in the 19F NMR spectra
of all fluoroquinolones demonstrates the existence of
Microanalyses were carried out on a CHNS-O model EA-
1102 elemental analyzer and were found to be in good
Table 2. 19F NMR spectral data for fluoroquinolones 11a–d in DMSO-d6
Compound
19F Chemical shifts, d (ppm) and coupling constants (Hz)
F6
F7
F8
CF3
11a
26.22 ddd
3JF6F7ˆ23.4 Hz
3JF6H5ˆ10.5 Hz
4JF6F8ˆ4.9 Hz
26.12 ddd
11.19 ddd
3JF7F6ˆ23.4 Hz
3JF7F8ˆ19.5 Hz
4JF7H5ˆ8.5 Hz
10.08 ddd
19.9 dm
90.18 dd
3JF8F7ˆ19.5 Hz
3J(CF3, HX)ˆ7.8 Hz
7J(CF3, F8)ˆ5.9 Hz
11b
20.76 m
21.95 m
21.99 m
90.49 dd
3JF6F7ˆ23.4 Hz
3JF6H5ˆ10.1 Hz
4JF6F8ˆ4.9 Hz
25.08
3JF7F6ˆ23.2 Hz
3JF7F8ˆ19.5 Hz
4JF7H5ˆ8.1 Hz
10.32 ddd
3J(CF3, HX)ˆ6.0 Hz
7J(CF3, F8)ˆ6.0 Hz
11c
96.36 dd
3JF6F7ˆ23.4 Hz
3JF6H5ˆ10.5 Hz
4JF6F8ˆ4.9 Hz
25.06 ddd
3JF7F6ˆ23.4 Hz
3JF7F8ˆ19.5 Hz
4JF7H5ˆ8.5 Hz
10.36 ddd
3J(CF3, HX)ˆ8.8 Hz
7J(CF3, F8)ˆ8.8 Hz
11d
96.60 dd
3JF6F7ˆ23.2 Hz
3JF6H5ˆ10.5 Hz
4JF6F8ˆ4.9 Hz
3JF7F6ˆ23.2 Hz
3JF7F8ˆ19.5 Hz
4JF7H5ˆ8.5 Hz
3J(CF3, HX)ˆ9.2 Hz
7J(CF3, F8)ˆ9.2 Hz

1926
A. Ya. Aizikovich et al. / Tetrahedron 56 (2000) 1923–1927
agreement with the calculated values. The compounds 1–34
and 97 were prepared as described previously.
JAXˆ4.3 Hz), 4.01 (dqd, 1H, CHXCF3, JAXˆ10.4, JBX
ˆ
4.3, JXFˆ8.0 Hz), 3.63 (m, 4H, CH2OCH2), 3.00–2.73 (m,
4H, CH2NCH2). 19F NMR: d 94.59 (d, CF3, JXFˆ8.0 Hz).
Anal. calcd for C7H11F3N2O3: C 36.8, H 4.9, N 12.3. Found:
C 36.8, H 4.8, N 12.1.
2-Benzoylamino-1,1,1-trifluoro-3-nitro-propane (4). Sus-
pension of 2 (13.90 g, 72 mmol), benzoyl chloride (12.08 g,
86 mmol) and dry pyridine (12.7 ml, 160 mmol) in 1,4-
dioxane (50 ml) was stirred at 40ЊC for 6 h. After cooling
of the mixture to room temperature, 50 ml cold water was
added and the crystalline residue was filtered off, washed
with 50 ml of hot water and dried. Yield 15.20 g (92%). Mp
158ЊC [Lit.10 158–159ЊC].
1,1,1-Trifluoro 3-nitro-2-piperidinopropane (7b) was
obtained similarly as an unstable yellow oil from the
diazo compound 3 and piperidine. Yield 61%. Bp 75–
76ЊC/5 mm. 1H NMR: d 4.66 (dd, 1H, CHAHBNO2,
JABˆ12.8, JAXˆ10.4 Hz), 4.50 (dd, 1H, CHAHBNO2, JAB
ˆ
12.8, JAXˆ4.3 Hz), 3.99 (dqd, 1H, CHXCF3, JAXˆ10.4,
JBXˆ4.3, JXFˆ8.2 Hz), 2.88–2.64 (m, 4H, CH2NCH2), 1.50
(m, 6H, (CH2)3). 19F NMR: d 94.46 (d, CF3, JHFˆ8.2 Hz).
3-Amino-2-benzylamino-1,1,1-trifluoropropane (5a). A
solution of the compound 4 (1.81 g, 7 mmol) in dry ether
(40 ml) was added dropwise to a suspension of LiAlH4
(1.59 g, 42 mmol) in dry ether, and the reaction mixture
was stirred for 8 h. After addition of 20% NaOH (10 ml)
the organic phase was separated, and the solvent was evapo-
rated to give a yellow oil which was fractionally distilled
under vacuum, yielding 0.99 g (65%) of 5a, as a colorless
oil, bp 104–105ЊC/2 mm. The compound was used imme-
diately for the syntheses of 5b and 11b.
1,1,1-Trifluoro-3-amino-2-morpholinopropane (8a) was
obtained from 7a according to the standard procedure
used for preparation of 5a. White hygroscopic oil. Yield
56%. Bp 71–72ЊC/5 mm. 1H NMR: d 3.68 (m, 4H,
CH2OCH2), 2.99 (dqd, 1H, CHXCF3, JAXˆ8.9, JBXˆ5.2,
JXFˆ8.2 Hz), 2.97–2.67 (m, 4H, CH2NCH2), 2.91 (dd, 1H,
CHAHBNH2, JABˆ12.8, JAXˆ8.9 Hz), 2.86 (dd, 1H,
CHAHBNH2, JABˆ12.8, JBXˆ5.2 Hz), 1.51 (br. s, 2H,
NH2). 19F NMR: d 94.33 (d, CF3, JHFˆ8.2 Hz). Anal.
calcd for C7H13F3N2O: C 42.4, H 6.6, N 14.1. Found: C
42.9, H 6.6, N 14.1.
2-Benzylamino-1,1,1-trifluoro-3-tosylaminopropane (5b).
A solution of tosyl chloride (1.71 g, 9 mmol) in pyridine
was added dropwise to a solution of 5a (0.99 g, 4.5 mmol)
in pyridine under cooling (0–5ЊC). The reaction mixture
was stirred for 2 h at ambient temperature, and after that
2% HCl (100 ml) was added. A precipitate of 5b was filtered
off and recrystallized from ethanol to yield 0.92 g (58%) of
5b as a white solid. Mp 108–109ЊC. 1H NMR: d 7.68 (d, 2H,
Ts, Jˆ8.2 Hz), 7.31 (c, 5H, Ph), 7.27 (d, 2H, Ts, Jˆ8.2 Hz),
5.07 (dd, 1H, CH2NH, Jˆ8.2, 3.3 Hz), 3.93 (d, 1H, CH2Ph,
Jˆ13.2 Hz), 3.37 (d, 1H, CH2Ph, Jˆ13.2 Hz), 3.41–2.75
(m, 4H, CHNH, CHCH2), 2.41 (s, 3H, CH3). 19F NMR: d
88.28 (d, CF3, JHFˆ7.3 Hz). Anal. calcd for C7H13F3N2O2S:
C 54.8, H 5.1, N 7.5. Found: C 55.1, H 5.2, N 7.5.
1,1,1-Trifluoro-3-amino-2-piperidinopropane (8b) was
obtained from 7b according to the standard procedure
used for preparation of 5a. Colorless hygroscopic oil.
1
Yield 31%. Bp 49–50ЊC/2 mm. H NMR: d 2.96 (dqd,
1H, CHXCF3, JAXˆ9.5, JBXˆ4.3, JXFˆ8.5 Hz), 2.91 (br.
m, 2H, CH2NCH2), 2.87 (dd, 1H, CHAHBNH2, JABˆ12.8,
JAXˆ9.5 Hz), 2.80 (dd, 1H, CHAHBNH2, JABˆ12.8,
JBXˆ4.3 Hz), 2.54 (br. m, 2H, CH2NCH2), 1.53 (m, 8H,
(CH2)3, NH2). 19F NMR: d 94.29 (d, CF3, JHFˆ8.5 Hz).
Anal. calcd for C8H15F3N2: C 49.0, H 7.7, N 14.3. Found:
C 49.0, H 7.7, N 14.2.
3-Amino-benzoylamino-1,1,1-trifluoropropane (6). Glycerol
(5.74 g, 62 mmol) was added to suspension of LiAlH4
(2.36 g, 62 mmol) in dry ether (50 ml) and was stirred for
1 h, then compound 4 (5.38 g, 21 mmol) was added. After
stirring for 6 h 20% NaOH was added and organic phase
was separated and evaporated. Oily residue was treated with
hexane and filtered to give 0.36 g (67%) of 6. Mp 74–
Ethyl 1-(2-benzoylamino-3,3,3-trifluoropropyl)-6,7,8-tri-
fluoro-4-oxoquinoline-3-carboxylate (11a). A mixture of
6 (0.75 g, 32 mmol) and 9 (1.04 g, 32 mmol) in toluene
(15 ml) was refluxed for 6 h. After addition of N-methyl-
morpholine (0.49 g, 48 mmol) the reaction mixture was
refluxed for 14 h, cooled and hexane was added. White
solid of 11a was filtered off, washed with 5 ml of hot isopro-
panol, and dried in air. Yield 0.57 g (36%). Mp 156–157ЊC.
Anal. calcd for C22H16F6N2O4: C 54.3, H 3.3, N 5.8. Found:
1
74.5ЊC. H NMR: d 7.91–7.79 (m, 2H, Ph), 7.58–7.43
(m, 3H, Ph), 7.37 (br. s, 1H, NHCOPh), 4.78 (m, 1H,
CHXCF3), 3.30 (dd, 1H, CHAHBNH2, JABˆ13.8, JAX
ˆ
3.8 Hz), 2.97 (ddq, 1H, CHAHBNH2, JABˆ13.8, JBXˆ5.1,
JHFˆ1.0 Hz), 1.36 (br.s, 2H, NH2). 19F NMR: d 87.52 (d,
CF3, JHFˆ7.3 Hz). Anal. calcd for C10H11F3N2O: C 51.7, H
4.8, N 12.1. Found: C 51,6, H 4.7, N 11.8. Evaporation of
hexane from the filtrate gave 36 mg of 5a (for characteristics
of 5a see the procedure given above).
C 54.0, H 3.3, N 5.6. H and 19F NMR spectral data are
1
given in Tables 1 and 2. 13C NMR in DMSO-d6: d 14.15
(CH3), 50.29 (CH, 2JCFˆ30.6, 5JCFˆ4.7 Hz), 53.57 (NCH2,
4JCFˆ14.2 Hz), 60.13 (OCH2), 108.88 (C-5, 2JCFˆ19.0 Hz),
1
109.74 (C-3), 124.12 (CF3, JCFˆ283 Hz), 124.69 (C-8a,
2JCFˆ5.3 Hz), 126.04 (C-4a), 127.37 (Cortho), 128.42
1
(Cmeta), 132.22 (Cpara), 132.55 (Cipso), 141.41 (C-8, JCFˆ
2
1
2
1,1,1-Trifluoro-2-morpholino-3-nitropropane (7a). To a
solution of morpholine (2.48 g, 29 mmol) in benzene
(25 ml) was added dropwise the diazo compound 3 in
benzene (25 ml). After stirring for 3 h the mixture was
evaporated and the residual yellow oil was fractionated
under vacuum to give 4.97 g (90%) of 7a. Bp 83–84ЊC/
238, JCFˆ14,5 Hz), 141.75 (C-7, JCFˆ255, JCFˆ17,5,
2JCFˆ15,3 Hz), 147.60 (C-6, JCFˆ250, JCFˆ10,6 Hz),
152.54 (C-2), 163.34 (O–CvO), 167.37 (N–CvO),
169.96 (C-4).
1
2
Ethyl 1-(2-benzylamino-3,3,3-trifluoropropyl)-6,7,8-tri-
fluoro-4-oxoquinoline-3-carboxylate (11b). A mixture of
5a (0.409 mg, 1.8 mmol) and 9 (0.60 g, 1.8 mmol) in
1
5 mm. H NMR: d 4.66 (dd, 1H, CHAHBNO2, JABˆ12.8,
JAXˆ10.4 Hz), 4.55 (dd, 1H, CHAHBNO2, JABˆ12.8,

A. Ya. Aizikovich et al. / Tetrahedron 56 (2000) 1923–1927
1927
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Resnati, G. Tetrahedron 1993, 49, 9385. (d) Fluorine-Containing
Amino Acids: Synthesis and Properties; Kuchar, V. P.; Soloshonok,
V. A., Eds; Wiley: Chichester, 1994. (e) Biomedical Frontiers of
Fluorine Chemistry; Ojima, I.; McCarthy, J. R.; Welch, J. T., Eds;
ACS: Washington, D.C., 1996. (f) Fluoroorganic Chemistry:
Synthetic Challenges and Biomedical Rewards; Resnati, G.;
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3. (a) Bouzard, D. In Antibiotics and Antiviral Compounds;
Krohn, K.; Rirst, H. A.; Maag, H. Eds.; VCH, Weinheim, 1993.
(b) Quinolone Antibacterial Agents; Hoope, D. C.; Wolfson, J. S.,
Eds.; ASM: Washington, 1993. (c) Lipunova, G. N; Mokrushina,
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Communications 1997, 109–110. (d) Lipunova, G. N.; Nosova,
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toluene was refluxed for 2 h. Toluene was evaporated and
the residue obtained was recrystallized from a mixture of
isopropanol and water (8:1). Yield 0.68 g (81%). Mp 120–
121ЊC. Anal. calcd for C22H118F6N2O3: C 55.9, H 3.8, N 5.9.
Found: C 55.7, H 3.8, N 5.9. 1H and 19F NMR spectral data
are given in Tables 1 and 2.
Ethyl 1-(2-morpholino-3,3,3-trifluoropropyl)-6,7,8-trifluoro-
4-oxoquinoline-3-carboxylate (11c) was obtained as a
white solid from 8a and 9. Yield 74%. Mp 202–203ЊC.
Anal. calcd for C19H18F6N2O4: C 50.4, H 4.0, N 6.2.
1
Found: C 50.2, H 4.1, N 6.1. H and 19F NMR spectral
data are given in Tables 1 and 2.
Ethyl 1-(2-piperidino-3,3,3-trifluoropropyl)-6,7,8-trifluoro-
4-oxoquinoline-3-carboxylate (11d). A mixture of 8b
(0.23 g, 12 mmol) and 9 (0.37 g, 12 mmol) in toluene
(10 ml) was refluxed for 2 h, toluene was evaporated and
the residue was recrystallized from isopropanol-water (8:1).
Yield 0.38 g (72%). Mp 169–17ЊC. Anal. calcd for
C20H20F6N2O3: C 53.3, H 4.5, N 6.2. Found: C 53.1, H
4.5, N 6.1. 1H and 19F NMR spectral data are given in Tables
1 and 2.
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1331–1332. (b) Aizikovich, A. Ya.; Korotaev, V. Yu.;
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Financial support of this research by the Russian Ministry of
Education is highly appreciated. It was fulfilled in the
frames of the program ‘Chemistry’, subprogram ‘Fine
organic synthesis’.
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