Attempted synthesis of ethyl 3,4-dihydro-2H-1, 4-benzoxazine-3-carboxylate and 3-acetate derivatives

Article abstract of DOI:10.1002/jhet.5570380133

Ethyl 3,4-dihydro-2H-1,4-benzoxazine-3-carboxylate derivatives 2 were obtained and isolated in low yields from the condensation of 2-aminophenol and ethyl 2,3-dibromopropanoate. They can be obtained by hydrogenation of ethyl 2H-1,4-benzoxazine-3-carboxyla

Full text of DOI:10.1002/jhet.5570380133

Jan-Feb 2001
Attempted Synthesis of Ethyl 3,4-Dihydro-2H-1,4-
benzoxazine-3-carboxylate and 3-Acetate Derivatives
Stanislas Mayer, Axelle Arrault, Gérald Guillaumet and Jean-Yves Mérour*
221
Institut de Chimie Organique et Analytique, associé au CNRS,
Université d'Orléans, BP 6759, 45067 Orléans Cedex 2, France
Received April 5, 2000
Ethyl 3,4-dihydro-2H-1,4-benzoxazine-3-carboxylate derivatives 2 were obtained and isolated in low
yields from the condensation of 2-aminophenol and ethyl 2,3-dibromopropanoate. They can be obtained by
hydrogenation of ethyl 2H-1,4-benzoxazine-3-carboxylate in satisfactory yield. Using 2-iminophenol did
not direct the condensation with ethyl 2,3-dibromopropanoate towards 2 but was fruitfull for the preparation
of ethyl 2-(4-benzyl-3,4-dihydro-2H-1,4-benzoxazin-3-yl)acetate from ethyl bromocrotonate.
J. Heterocyclic Chem., 38, 221 (2001).
The 3,4-dihydro-2H-1,4-benzoxazine framework is often
So the direct condensation of ethyl 2,3-dibromo-
propanoate with 2-substituted aminophenols always led to
benzoxazines 1. Since structures of type 2 correspond to
strained aminoacid, it would be of interest to develop new
methods to reach these structures.
encountered in pharmacologically active compounds [1]. In
our group we have developped inter alia the synthesis of new
calcium antagonists [2] and new imidazolinic derivatives [3]
having this skeleton. Ethyl 3,4-dihydro-2H-1,4-benzoxazine-
2-carboxylate was the starting material to enter in this series.
Usually the synthesis of 3,4-dihydro-2H-1,4-benzox-
azine-2-carboxylate was performed by treating 2-amino-
phenol with ethyl 2,3-dibromopropanoate to afford the
benzoxazinic compound 1a [4] and not the isomeric
derivative 2a (Scheme 1).
One approach to prepare 2 was to start from 1,4-benzox-
azine derivatives, introducing at the correct position an
ester group; an other was to generate the ester function by
modification of a 3-functional group already present on the
2,3-dihydro-1,4-benzoxazine moiety. The first approach
was illustrated with the benzoxazinic derivative 7. Coudert
et al. [8] have reacted ethyl chloroformate with the lithio
derivative of benzoxazine 7 to afford the ethyl 1,4-benzox-
azine-3-carboxylate 8 which was a very good precursor for
compounds 2 (Scheme 3). Thus the catalytic hydrogena-
tion of 8 in ethanol over palladium on carbon (Pd/C) gave
the desired ethyl 3,4-dihydro-2H-1,4-benzoxazine-3-car-
boxylate 2d in 49% yield; this reduction was reluctant in
our conditions: 50 atm, 25% weight of palladium, 3 days at
room temperature. The nmr data of 2d were consistent
with the structure and different from compound 1d [9].
The second approach to compounds 2 was the oxidation
of products having an hydroxymethyl group at the
The influence of the substitution on the nitrogen atom of
the starting aminophenol (R = CH , R = Ts) has been
3
investigated [1c,5,6]. In all cases the structures 1b,c were
obtained; Bartsch [5] has demonstrated that the correct
structure for the 2,3-dihydro-1,4-benzoxazine obtained
from the 2-N-tosylaminophenol is 1c and not 2c [6].
For our own part we have reacted 7-hydroxyindoline 5
[7], which may be considered as 2-aminosubstituted
phenol, with ethyl 2,3-dibromopropanoate to obtain
(Scheme 2) compound 6 in 83% yield which structure has
been unambigously determined by 2D NMR assignement.
3-position such as in compound 9 [10]. The use of Dess-
TM
Martin periodinate reagent, Magtrieve
reagent,
potassium permanganate and Swern oxidation led only to
degradation products (Scheme 4).
Although oxidation of 9 was fruitless, more success has
been achieved by Bartsch in the hydrolysis of the nitrile
group of compound 10 [5] which afforded (Figure 1) the
required ester 2c (68% yield).
Nevertheless, within our hand, the deprotection of the
nitrogen atom of 2c afforded degradation products; so we
decided to carefully investigate the condensation of various

222
S. Mayer, A. Arrault, G. Guillaumet and J.-Y. Mérour
Vol. 38
substituted 2-aminophenols 11 with ethyl 2,3-dibromo-
propanoate using potassium carbonate as base in acetone at
reflux (Scheme 5). From 11a we can isolate after tedious
chromatographic separation, in low yield (4%), the
''inverse'' benzoxazine 2a from the normal benzoxazine 1a
which is produced in high yield. With substituted
aminophenols 11e-g the yields of benzoxazines 2 slightly
increased, but were still low (see Table 1). Compounds 2
were relatively unstable and thus they were treated with
iodomethane in the presence of potassium carbonate to
afford in moderate yield the N-methyl derivatives 12.
More experiments were carried out in order to increase
the yield of compounds 2: use of a mixture of 2-propanol/-
acetone 1:99 or 50:50 v/v, addition of water, replacement
of potassium carbonate with potassium hydrogeno-
carbonate; all these modifications were not conclusive.
It was thus possible to obtain benzoxazine 2 in low yield
by direct condensation of 2-aminophenol. Compounds 2
might result either from a Michael addition on ethyl
2-bromoacrylate, generated in situ, or from a direct
displacement of a bromine atom by the oxygen atom rather
than the nitrogen atom of the 2-aminophenol.
1
The assignements for structures 2 were based on H nmr
13
and C nmr data which are reported in the Table 2 and
Table 3. As an illustrative example the chemical shifts for
carbon C-2 and for C-3 in compound 2e were 65.6 ppm
and 53.1 ppm respectively; while for compound 1e the
chemical shifts for the same carbons were respectively
1
72.4 ppm and 42.3 ppm. The H NMR spectra indicated
inter alia a chemical shift for the angular proton of 2e
equal to 4.10 ppm compared to 4.67 ppm for 1e.

Jan-Feb 2001
Attempted Synthesis of Ethyl 3,4-Dihydro-2H-1,4-benzoxazine-3-carboxylate
223
Table 1
Yield (%)
a
e
f
g
1
2
12
81
4
-
74
13
44
51
9
38
68
13
45
We have envisaged to direct the reaction towards the
formation of benzoxazines 2 by masking or decreasing the
nucleophilicity of the nitrogen atom of the 2-aminophenol.
This approach has been described using trifluoroacetyl or
p-toluenesulfonyl group as withdrawing groups on the
nitrogen atom for the preparation of ethyl 2-(4-tosyl-3,4-
dihydro-2H-1,4-benzoxazin-3-yl)acetate 4c [11]. Since the
use of the p-toluenesulfonyl group was unfruitfull for
obtaining 2c [5] we planned to use an imine as the
precursor of the amino group. We first tested this approach
in the synthesis of ethyl 2-(4-benzyl-3,4-dihydro-2H-
1,4-benzoxazin-3-yl)acetate 4e (Scheme 6).
The aminophenol 11a reacted with benzaldehyde to
afford the imine 13 [12] which was treated with ethyl
bromocrotonate to afford imine 14. The in situ reduction of
14 with sodium borohydride in isopropanol gave the
corresponding amine which spontaneously undergoes an
intramolecular Michael addition to afford the benzoxazine
4e in a global yield of 65%. During the reduction, a small
amount of compound 15 was formed and isolated in 8%
yield (Figure 2). Application of this imine methodology
for the synthesis of compounds 2 resulted in a mixture of
products. The usual isomeric benzoxazine 3e [13] was
produced in satisfactory yield by an initial reduction of
imine 13 to the 2-benzylaminophenol, followed by
condensation with ethyl bromocrotonate.
In conclusion we have described the formation of
3,4-dihydro-2H-1,4-benzoxazine-3-carboxylate during the
synthesis of 3,4-dihydro-2H-1,4-benzoxazine-2-
carboxylate. Using a precursor that posseses the ethoxy-
carbonyl group in position-3 of the benzoxazine
framework, the obtention of 2 was easy.
Table 2
H NMR δ (deuteriochloroform) J (Hz)
1
Compound
2a
H
H
OCH CH
3
Other
ArH
2
3
2
4.24 (dd, 1H, J = 6.0, 10.5)
4.44 (dd, 1H, J = 3.1, 10.5)
3.53 (dd, 1H, J = 3.2, 11.2)
4.58 (dd, 1H, J = 1.8, 11.2)
4.13 (dd, 1H,
J = 3.1, 6.0)
5.14 (dd, 1H,
J = 1.8, 3.2)
4.25 (q, 2H, J = 7.1, CH )
1.30 (t, 3H, J = 7.1, CH )
4.15 (q, 2H, J = 7.1, CH )
1.17 (t, 3H, J = 7.1, CH )
4.31 (br s, 1H, NH)
6.64-6.72 (m, 2H);
6.78-6.83 (m, 2H).
6.78 (dd, J = 1.7, 7.9,
1H); 6.93-7.00 (m, 2H);
7.26 (d, 2H, J = 8.3);
7.60 (d, 2H, J = 8.3);
7.81 (dd, 1H,
2
3
2c[5b]
2.39 (s, 3H, CH )
3
2
3
J = 1.6, 8.3).
2d
2e
2f
4.13-4.24 (m, 1H)
5.15 (br s, 1H)
4.24 (q, 2H, J = 7.1, CH )
1.56 (s, 9H, CH )
6.88-6.98 (m, 3H);
2
3
4.70 (dd, 1H, J = 1.9, 11.9)
4.22 (dd, 1H, J = 5.5, 10.5);
4.37 (dd, 1H, J = 3.1, 10.5)
4.01-4.28 (m, 2H)
1.22 (t, 3H, J = 7.1, CH )
8.14 (br s, 1H, H ).
3
5
4.10 (dd, 1H,
J = 3.1, 5.5)
4.05 (dd,1H,
J = 3.2, 5.1)
4.08 (dd, 1H,
J = 3.1, 6.0)
4.21(q, 2H, J = 7.2, CH )
2.19 (s, 3H, CH )
6.43-6.50 (m, 2H);
6.68 (d, 1H, J = 7.9).
6.12-6.26 (m, 2H);
6.62 (d, 1H, J = 8.5).
6.37 (s, 2H).
2
3
1.28 (t, 3H, J = 7.2, CH )
4.32 (br s, 1H, NH)
3
4.23 (q, 2H, J = 7.0, CH )
3.68 (s, 3H, OCH )
2
3
1.22 (t, 3H, J = 7.0, CH )
4.50 (br s, 1H, NH)
3
2g
4.17 (dd, 1H, J = 6.0, 11.0)
4.40 (dd, 1H, J = 3.1, 11.0)
4.21 (q, 2H, J = 7.0, CH )
2.12 (s, 3H, CH );
2
3
1.27 (t, 3H, J = 7.0, CH )
2.18 (s, 3H, CH );
3
3
4.35 (br s, 1H, NH)
12e
12f
3.97 (t,1H, J = 2.3)
4.15-4.21 (m, 1H)
3.95 (t, 1H, J = 2.5)
4.13-4.20 (m,1H)
4.57 (dd, 1H,
J = 2.3, 10.8)
4.55 (dd, 1H,
J = 2.5, 10.7)
4.23 (q, 2H, J = 7.0, CH )
2.27 (s, 3H, CH )
6.42-6.50 (m, 2H);
6.65 (d, 1H, J = 7.8).
6.15 (dd, 1H,
2
3
1.25 (t, 3H, J = 7.0, CH )
2.98 (s, 3H, NCH )
3
3
4.22 (q, 2H, J = 7.0, CH )
2.96 (s, 3H, NCH )
3
2
1.28 (t, 3H, J = 7.0, CH )
3.75 (s, 3H, OCH )
J = 2.8, 8.6);
3
3
6.27 (d, 1H, J = 2.8);
6.67 (d, 1H, J = 8.6).
6.33-6.36 (m, 2H).
12g
3.96 (t, 1H, J = 2.1)
4.62 (dd, 1H,
4.20 (q, 2H, J=7.0, CH )
2.11 (s, 3H, CH );
3
2
4.15-4.25 (m, 1H)
J = 2.1, 10.7)
1.25 (t, 3H, J = 7.0, CH )
2.23 (s, 3H, CH );
3
3
2.97(s, 3H, NCH )
3

224
S. Mayer, A. Arrault, G. Guillaumet and J.-Y. Mérour
Vol. 38
Table 3
13
C NMR, Mass Spectra and IR Spectral Data of Compounds 2, 12
13
Compound Molecular
Formula
C NMR δ (deuteriochloroform)
Mass
Spectra
(M+1)
IR (film)
(cm )
-1
+
C
C
CO
ArCH
ArC
Other
OCH CH
2 3
2
3
2a
C
H
NO
67.5 53.2 170.5
64.2 55.8 167.8
116.2, 117.0,
119.4, 122.2
117.6, 121.8,
123.9, 125.9,
127.4(2), 130.2(2)
117.4(2), 121.9,
124.1
116.4, 116.7,
119.7
101.8, 104.6,
117.4
132.2, 143.6
62.0, 14.4
62.3, 14.1
208
362
3379, 1741
11 13
3
2c[5b]
C
H
NO S
123.4, 135.8,
144.8, 145.9
21.8 (CH )
1756, 1360,
1158
18 19
5
3
2d
2e
C
H
NO
NO
NO
NO
NO
NO
NO
66.1 56.0 169.3
152.6
65.6 53.1 170.5
126.4, 145.7
28.6(3×CH )
82.7 (C)
62.1, 14.5
61.8, 14.2
62.0, 14.5
61.2, 14.3
61.1, 14.1
61.3, 14.2
61.2, 14.5
308
222
238
236
236
252
250
1749, 1660
3300, 1748
3300, 1744
3300, 1747
1754
16 21
5
3
4
3
3
4
3
3
C
C
C
C
C
C
H
131.4,
131.7, 141.3
133.0,
138.0, 151.1
125.9, 130.7,
131.3, 139.6
130.9,
139.5, 142.2
135.6,
21.2 (CH )
12 15
3
2f
H
65.9 53.5 170.4
65.7 53.3 170.7
65.6 61.0 171.8
65.5 60.8 169.4
65.9 60.6 170.7
55.8 (OCH )
3
12 15
2g
H
114.3, 121.7
15.6(CH )
3
13 17
20.8 (CH )
3
12e
12f
12g
H
114.8, 115.2,
125.7
98.8, 101.0, 115.8
21.0 (CH )
13 17
3
39.7 (NCH )
3
H
37.7 (NCH )
1756
13 17
3
137.6, 155.1
125.0, 130.7:
134.5, 139.7
55.5 (CH )
3
H
110.4, 120.2
16.0 (CH )
1757
14 19
3
21.3 (CH )
3
38.3 (NCH )
3
EXPERIMENTAL
After filtration and evaporation in vacuo the residue was
separated on silica gel using ethyl acetate/petroleum ether 3:7 to
give an oil; 113 mg (49%).
1
13
Both H NMR and C NMR spectra were obtained with a
Bruker instrument Avance DPX250 (250 MHz); for samples in
deuteriochloroform solution with tetramethylsilane as internal
standard, chemical shifts (δ values) were reported in parts per
million and coupling constants (J values) in Hz. The IR spectra
were recorded as a thin film on sodium chloride plates for the oils
and in a potassium bromide pellet for solids on a Perkin-Elmer
spectrometer FT Par agon1000 PC. Mass spectra were recorded
on a Perkin-Elmer mass spectrometer SCIEX API 300 (ionspray
or heat nebuliser). Melting points were measured using a Kofler
hot stage apparatus and are uncorrected. Flash column
chromatography was performed on silica gel (Merck 60,
230-400 mesh). Thin layer chromatography was performed on
pre-coated silica gel plates (Merck 60, F254, 0.25mm). The
solvents were HPLC grade.
Anal. Calcd. for C
Found: C, 62.25; H, 7.01; N, 4.73.
H NO : C, 62.53; H, 6.89; N, 4.56.
16 21 5
Ethyl 2-(4-Benzyl-3,4-dihydro-2H-1,4-benzoxazin-3-
yl)acetate (4e).
A mixture of ethyl 4-bromocrotonate (0.52 ml, 2.83 mmoles),
potassium carbonate (719 mg, 5.21 mmoles) and imine 13 [12]
(505 mg, 2.56 mmoles) in ethanol (6 ml) was stirred at room
temperature for 3 days. After filtration and evaporation the
residue was dissolved in ethanol (18 ml); silica gel (2.10 g) was
added and the mixture was cooled at 0 °C. Sodium borohydride
(261 mg, 6.83 mmoles) was portionwise added in 15 minutes and
the mixture was stirred for 30 hours at room temperature. The
mixture was filtrated over filter aid and evaporated in vacuo;
water was added and the mixture was extracted with ethyl
acetate; the organic layers were dried over magnesium sulfate
and evaporated. The residue was separated on silica gel
(petroleum ether/ethyl acetate 75:25) to afford 4e as white solid
(518 mg, 65%); mp 57 °C (ethyl acetate). IR (potassium
General Procedure for the Synthesis of Compounds 2.
To a stirred suspension of 2-aminophenol 11 (18 mmoles) and
potassium carbonate (50 mmoles) in acetone (100 ml) was added
ethyl 2,3-dibromopropanoate (19.8 mmoles). The mixture was
refluxed for 18 hours. After filtration the filtrate was concen-
trated in vacuo to give a residue which was separated twice on
silica gel using ethyl acetate/petroleum ether 7:3 as eluent to give
first compound 1 and then compound 2.
-1
1
bromide): ν (cm ) 1723 (CO). H nmr (deuteriochloroform): δ
1.22 (t, 3H, J = 7.1Hz, CH ); 2.58 (dd, 1H, J = 5.1Hz, 16.1Hz,
3
CH CO); 2.71(dd, 1H, J = 8.4Hz, 16.1Hz, CH CO); 3.83-3.89
2
2
(m, 1H, CH), 4.03-4.16 (m, 1H, CH O); 4.09 (q, 2H, J = 7.1Hz,
2
OCH ); 4.27 (dd, 1H, J = 4.3Hz, 10.9Hz, CH O); 4.43 (d, 1H,
2
2
J = 16.5Hz, NCH ); 4.54 (d, 1H, J = 16.5Hz, NCH ); 6.57-6.67
2
2
4-(tert-Butyl)-3-ethyl-3,4-dihydro-2H-1,4-benzoxazine-3,4-
dicarboxylate (2d).
(m, 2H, Harom); 6.75-6.87 (m, 2H, Harom); 7.22-7.37 (m, 5H,
13
Harom). C nmr (deuteriochloroform): δ 14.3 (CH ); 35.1
3
To a solution of compound 8 [8] (230 mg, 0.64 mmole) in
ethanol (25 ml), palladium on charcoal/10% (70 mg) was
added. Hydrogen was admitted in the pressure steel vessel
(50 atm) and the mixture stirred at room temperature for 3 days.
(CH ); 53.6 (CH); 54.4 (CH ); 60.9 (CH ); 66.7 (CH ); 113.5
2
2
2
2
(CH); 116.6 (CH); 117.9 (CH); 122.2 (CH); 127.0 (2CH); 127.4
(CH); 128.9 (2CH); 133.9 (C); 138.3 (C); 143.5 (C); 171.8 (CO);
+
ms: (ionspray) m/z 312 (M+1) .

Jan-Feb 2001
Attempted Synthesis of Ethyl 3,4-Dihydro-2H-1,4-benzoxazine-3-carboxylate
225
REFERENCES AND NOTES
Anal. Calcd. for C
H NO : C, 73.29; H, 6.80; N, 4.50.
19 21 3
Found: C, 72.92; H, 6.94; N, 4.67.
[*] Author E-mail: jean-yves.merour@univ-orleans.fr; Fax: (33)
2-38-41-70-81.
Ethyl 2,3,5,6-Tetrahydro[1,4]oxazino[2,3,4-hi]indole-2-
carboxylate (6).
[1a] C. Banzatti, A. D. Torre, P. Melloni, D. Pieraccioli and P.
Salvadori, J. Heterocyclic Chem., 20, 139 (1983); [b] R. C. M. Butler, C.
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Chem., 42, 5043 (1999).
Using the general procedure as for 2, starting from 7-hydroxy-
indoline 5 [7], compound 6 was obtained in 83% yield. IR (film):
-1
1
ν (cm ) 1753 (CO); H nmr (pyridin-d , 400 MHz): δ 1.15 (t, 3H,
5
J = 7.0Hz, CH ); 2.70-2.78 (m, 2H, H ); 2.89 (q, 1H, J = 8.9Hz,
3
6
H ); 3.03 (dd, 1H, J = 2.8Hz, 12.0Hz, H ); 3.22-3.28 (m, H, H );
5
3a
5
3.49 (dd, 1H, J = 4.3Hz, 12.0Hz, H ); 4.09-4.17 (m, 2H, J = 7.0Hz,
3b
OCH ); 5.23 (dd, 1H, J = 2.8Hz, 4.3Hz, H ); 6.67-6.75 (m, 2H,
2
2
13
Harom); 6.90-6.95 (m, 1H, Harom). C nmr (deuteriochloroform):
δ 15.0 (CH ); 30.2 (CH ); 49.5 (CH ); 56.9 (CH ); 62.5 (CH ); 75.2
3
2
2
2
2
(CH); 113.7 (CH); 118.0 (CH); 121.6 (CH); 131.1 (C); 138.6 (C);
+
[2] A.-S. Bourlot, I. Sanchez, G. Dureng, G. Guillaumet, R.
Massingham, A. Monteil, E. Winslow, M. D. Pujol and J.-Y. Mérour, J.
Med. Chem., 41, 3142 (1998).
142.7 (C); 170.2 (CO); ms: (ionspray) m/z 234 (M+1) .
Anal. Calc. For C H NO : C, 66.94; H, 6.48; N, 6.00. Found
13 15
3
C, 67.33; H, 6.29; N, 5.81.
[3] N. Baurin, C. Marot, L. Morin-Allory, J.-Y. Mérour, G.
Guillaumet, M. Payard and P. Renard, J. Med. Chem., 43, 1109 (2000).
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(1983); [b] H. Bartsch, Monatsh. Chem. 118, 273 (1987).
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J. McLoughin, A. Mitchell, B. S. Slatcher, L. H. Smith and M. A.
Stevens, J. Med. Chem., 15, 49 (1972).
[7] W. G. Gall, B. D. Astill and V. Boekelheide, J. Org. Chem.,
20, 1538 (1955).
[8] L. Chacun-Lefebvre, C Buon, P. Bouyssou and G. Coudert,
Tetrahedron Lett., 39, 5763 (1998).
[9] We thank Dr. C. Buon (University of Orleans) for a sample of
compounds 1d and 7.
[10] G. W. H. Potter and A. M. Monro, J. Heterocyclic Chem., 9,
299 (1972).
General Procedure for Methylation of Compounds 2:
Compounds 12.
A stirred suspension of compound 2 (10 mmoles), potassium
carbonate (30 mmoles), iodomethane (30 mmoles) in acetone
(75 ml) was refluxed for 18 hours. After filtration, the filtrate was
concentrated in vacuo to give a residue which was twice
separated on silica gel using ethyl acetate/petroleum ether 7:3 as
eluent to give compound 12.
Ethyl 4-[2-(Benzylamino)phenoxy]butanoate (15).
This compound was obtained from the reduction of 14 in 8%
-1
1
yield as an oil. IR (film): ν (cm ) 3425 (NH), 1733 (CO). H nmr
(deuteriochloroform): δ 1.23 (t, 3H, J = 7.2Hz, CH ); 2.09-2.19
3
(m, 2H, CH ); 2.49 (t, 2H, J = 6.5Hz, CH ); 4.05 (t, 2H, J =
2
2
6.5Hz, OCH ); 4.10 (q, 2H, J = 7.2Hz, OCH ); 4.37 (s, 2H, CH );
2
2
2
4.68 (br s, 1H, NH); 6.55-6.67 (m, 2H, Harom); 6.75-6.84 (m, 2H,
13
Harom); 7.23-7.40 (m, 5H, Harom). C nmr (deuterio-
chloroform): δ 14.4 (CH ); 24.9 (CH ); 31.3 (CH ); 48.1 (CH );
3
2
2
2
60.7 (CH ); 67.4 (CH ); 110.4 (CH); 110.6 (CH); 116.7 (CH);
2
2
121.6 (CH); 127.2 (2CH); 127.5 (CH); 128.8 (2CH); 138.4 (C);
+
139.9 (C); 146.0 (C); 173.4 (CO); ms: (ionspray) m/z 314 (M+1) .
[11] P. H. Williams, L. Zard, T. A. Purcell, D. Galtier, J.-C; Muller,
P. George, J. Frost, P. Pasau, C. Rousselle and R. Bartsch, Eur. Patent
0614893 (1994); Chem. Abstr. 123, 169634d (1995).
Anal. Calcd. for C
H NO : C, 72.82; H, 7.40; N, 4.47.
19 23 3
Found: C, 72.96; H, 7.29; N, 4.60.
[12] T. J. Lane and A. J. Kandathil, J. Am. Chem. Soc., 83, 3783
(1961).
Acknowledgement.
Financial support of this work by ADIR (Courbevoie, France)
is gratefully acknowledged.
[13] Y. Masuoka, T. Asako, G. Goto and S. Noguchi, Chem.
Pharm. Bull., 34, 130 (1986).