Unnatural amino acids. 2. Simple method of obtaining esters of aziridine-2-carboxylic acids by a transesterification reaction

Article abstract of DOI:10.1023/B:COHC.0000040767.96090.cc

A series of N-unsubstituted esters of aziridine-2-carboxylic acid has been obtained by transesterification in basic medium using primary, secondary, and tertiary alcohols. Methods of transesterification using various bases (K ₂CO₃, R

Full text of DOI:10.1023/B:COHC.0000040767.96090.cc

Chemistry of Heterocyclic Compounds, Vol. 40, No. 6, 2004
UNNATURAL AMINO ACIDS.
2*. SIMPLE METHOD OF OBTAINING ESTERS
OF AZIRIDINE-2-CARBOXYLIC ACIDS BY
A TRANSESTERIFICATION REACTION
B. Shtrumfs, D. Chernyak, I. Kums, I. Kalvins, and P. Trapencieris
A series of N-unsubstituted esters of aziridine-2-carboxylic acid has been obtained by transesterification
in basic medium using primary, secondary, and tertiary alcohols. Methods of transesterification using
various bases (K2CO3, ROLi, t-BuOK) have been compared. Transesterification with lithium alcoholates
also affords the possibility of obtaining esters of N-substituted aziridine-2-carboxylic acids.
Transesterification of chiral esters proceeds with retention of the configuration of the chiral center.
Keywords: diastereomers, esters of aziridine-2-carboxylic acid, enantiomers, transesterification.
Esters of aziridine-2-carboxylic acid are a convenient source of various derivatives of α- and β-amino
acids, due to the high reactivity of the aziridine ring [2,3]. In difference to esters of other amino acids, aziridine-
2-carboxylates have no tendency to dimerize, consequently the direct transesterification method may be used in
the aziridine-2-carboxylate series.
The transesterification of aziridine-2-carboxylates has not been described in the literature, although good
results have been obtained for compounds of other classes [4] on using acid or base catalysis, catalysis by
alcoholates [4-7], organotin [8] and organotitanium compounds [9], and also indium triiodide [10]. To obtain
aziridine-2-carboxylates we chose the base catalysis method [4,5] since aziridines are unstable under acid
conditions and in the presence of strong Lewis acids. Lithium alcoholates, used in [5], are readily obtained from
the corresponding alcohols by reaction with butyllithium. As starting materials we used aziridine-2-carboxylic
acid methyl ester 1, for which a convenient method of synthesis has been developed [1], and its 1-alkyl and
1-acyl derivatives obtained by known methods used for the protection of the amino group of amino acids [11].
We have obtained a series of N-unsubstituted aziridine-2-carboxylates 2a-h, using primary, secondary,
and tertiary alcohols, and have compared two methods (A and B) of transesterification. The transesterification
products were obtained in high or moderate yields (Table 1).
O
O
A: ROH, 20 mol %> K2CO3, 90-120°C
B: ROH, n-BuLi, THF, -20°C–room temp
OR
OMe
N
H
N
H
1
2a–h
_______
* For Part 1 see [1].
__________________________________________________________________________________________
Latvian Institute of Organic Synthesis, Riga LV-1006; e-mail: boriss@osi.lv. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 6, pp. 850-859, June, 2004. Original article submitted March 23, 2004.
0009-3122/04/4006-0725©2004 Plenum Publishing Corporation
725

TABLE 1. Yields of Esters 2a-h Synthesized by Methods A and B
Method A
Method B
Ester
Reaction
time, h
Yield,
%*
Reaction
time, h
Yield,
%*
2a
2b
24
41
1
30
O
O
N
H
O
2
32
48
<1
O
N
H
NO2
O
2c
2
40
5
2
4
O
N
H
O
2d
24
78*
45
O
N
H
2e
240
0
1
67
O
O
N
H
O
2f
100
100
0
0
1
1
80
39
O
N
H
O
2g
O
N
H
HO
O
2h
100
0
1
57
O
N
H
O
_______
* According to data of gas chromatography.
726

Method A is based on catalysis by K2CO3 base and by the shift in chemical equilibrium in the direction
of forming reaction products by distilling out the more volatile alcohol MeOH. Reaction was carried out without
solvent. In method B [5] the appropriate lithium alcoholate was used as reagent, generated with butyllithium in
situ from the corresponding alcohol.
Comparison of methods A and B showed that catalysis by a weak base (K2CO3) gives satisfactory yields
of esters only with primary alcohols of the benzyl and allyl types (esters 2a-d). In the case of perillyl alcohol
(ester 2d) the reaction proceeds by method A (according to data of gas chromatography the yield was 78%), but
the ester was not isolated successfully due to side product formation. The 4-nitrobenzyl ester 2b was
successfully obtained only by method A. This is not unexpected since the incompatibility of organolithium bases
with nitro compounds is known.
In the case of the more sterically hindered alcohols (esters 2e-h) the transesterification proceeds only by
method B, since the alcoholates of secondary and tertiary alcohols are more strongly basic than K2CO3. This
method enables acylation of alcoholic groups of complex molecules such as steroids, particularly of estradiol
derivatives (esters 2g,h). Acylation in the case of estradiol (ester 2g) occurs regioselectively only at the alicyclic
and not at the phenolic hydroxyl, although for deprotonation both alcoholic groups use 2 equivalents of BuLi.
Attempts to carry out the transesterification reaction with polyhydric alcohols (glycerol, pentaerythritol,
diacetonylglucose) did not give the expected reaction products. When using these alcohols in method A a
mixture of aziridine ring fission products was obtained, on using the corresponding lithium alcoholates
(method B), only starting materials were obtained.
Transesterification with lithium alcoholates also enables esters of the N-substituted aziridine-2-
carboxylic acids 4a-j to be obtained from the corresponding methyl esters (Table 2).
O
O
OR
ROH, n-BuLi, THF, -20°C–room temp.
OMe
N
X
N
X
4a–i
3a–i
The reaction of lithium alcoholates with N-alkyl derivatives of aziridine-2-carboxylic acid methyl ester
3a-d proceeds smoothly with yields of esters 4a-d of 41-88%. The steric effects of the substituent at the nitrogen
atom proved to have no significant effect on the course of the reaction. Transesterification of methyl esters is the
most convenient route to obtain esters 4c,d, since alkylation of esters 2e,f with benzyl and trityl chlorides
proceeds slowly and with the formation of side products. The use in this reaction of the corresponding bromides
is undesirable due to the higher nucleophilicity of bromide ion, which leads to fission of the aziridine ring even
at room temperature.
It was shown that the diastereomers of the (-)-menthyl ester of N-benzylaziridine-2-carboxylic acid 4c
and 4'c may be separated chromatographically. In the case of the N-unsubstituted compounds 2e the
diastereomers are not separable. It was also established that the asymmetric center C(2) of the aziridine ring is not
racemized on transesterification. The optically pure ester R-1 [1], obtained from the methyl ester of L-serine by
the Mitsunobu reaction [12], on transesterification with lithium tert-butylate by method B gives ester R-2f.
Comparison of the N-benzyloxycarbonyl derivative of this ester R-4f, obtained by the standard method [11],
with the racemic ester R,S-4f by HPLC on a chiral column (enantiomer retention times 9.3 and 10.5 min) showed
that ester R-4f (retention time 9.3 min) is enantiomerically pure.
727

TABLE 2. Yields of Esters 4a-j
Ester
Reaction time, h
1
Yield, %
88
O
4а
O
N
O
O
4b
1
3
79
48
O
N
4c
O
O
N
O
4d
3
1
41
65
O
N
O
4e
O
N
O
O
N
O
4f
1
1
15
21
O
O
O
O
4g
O
O
N
O
O
4h
4i
1
2
2
71
76
56
O
N
O
O
O
O
N
O
O
O
4j
O
N
O
N
728

O
O
O
O
t-BuOH, n-BuLi, THF, -20°C–rom temp.
H
N
H
H
N
H
80%
R-1
R-2f
O
CBz–Cl, Et3N,
CH2Cl2, -5°C – room temp, 1 h
O
H
N
96%
O
O
R-4f
Transesterification of the corresponding methyl esters of N-acylaziridine-2-carboxylic acid 3e-j also
enables the preparation of the series of esters of N-acyl aziridine-2-carboxylic acid 4e-j. Satisfactory yields were
observed when the substituent at the nitrogen atom was identical to the ester group (esters 4e,h). On
transesterification of the methyl ester of N-benzyloxycarbonylaziridine-2-carboxylic acid 3f with lithium
tert-butylate a 1:1 mixture of esters 4f and 4h was formed. Ester 4h is formed by transacylation at the nitrogen
atom of the aziridine ring, consequently esters 4f and 4g are conveniently obtained by the N-acylation of esters
2f and 2a respectively. In the case of the carbamoyl derivative 4j the transesterification reaction proceeds
smoothly (56%). The tert-butyl carbamate group of ester 3i is also not subject to a transacylation side reaction,
and also provides a good yield of ester 4i.
TABLE 3. 1H NMR Spectra of Aziridine-2-carboxylic Acid Esters 2a-h and
4a-n
O
OR
N
X
Com-
pound
X
R
1H NMR spectrum (CDCl3), δ, ppm (J, Hz)
1
2
3
4
2a
H
Bn
1.09 (1H, br. s, NH); 1.74-1.93 (1H, m, H-3);
1.93-2.08 (1H, m, H-3); 2.47-2.63 (1H, m, H-2);
5.18 (2H, s, СН2Ph); 7.30-7.41 (5H, m, arom.)
2b
2c
H
H
4-NO2–
С6Н4CH2
1.11 (1H, br. s, NH); 1.71-2.06 (2H, m, H-3);
2.40-2.64 (1H, m, H-2); 5.22 (2H, s, CH2Ph);
7.76 (2H, d, J = 9.0, o-H arom.); 8.22 (2H, d,
J = 9.0, m-H arom.)
Allyl
1.08 (1H, br. s, NH); 1.78-2.12 (2H, m, H-3);
2.48-2.65 (1H, m, H-2);
4.63-4.71 (2H, m, CH2–CН=CH2);
5.24–5.43 (2H, m, CH2–CН=CH2);
5.84-6.06 (1H, m, CH2–CН=CH2)
729

TABLE 3 (continued)
1
2
3
4
2d
2e
H
Perillyl
1.07 (1H, br. s, NH); 1.35-2.26 (9H, m, aliph.);
1.74 (3H, s, CH3); 2.50-2.60 (1H, unresolved dd,
H-2); 4.47-4.64 (2H, m, OCH2); 4.68-4.80 (2H, m,
C=CH2); 5.75-5.86 (1H, m, aliph.)
H
Menthyl
0.76 and 0.77 (3H, d and d,
menthyl CH3); 0.79-1.16 (4H, m, aliph.);
0.91 (6H, d, = 6.5, -Pr); 1.31-2.07 (9H, m, aliph.);
4.73 (1H, ddt, 3J = 2.2, 3J = 4.5, 3J = 10.8, OCH)
0.96 (1H, br. s, NH); 1.48 (9H, s, -Bu);
J = 7.0 and J = 7.0,
J
i
2f
H
H
t-Bu
t
1.70-1.84 (1H, m, H-3); 1.86-1.98 (1H, m, H-3);
2.33-2.47 (1H, m, H-2)
2g
Estradiolyl
0.85 (3H, s, CH3); 1.08-2.38 (15H, m, aliph., NH);
2.55 (1H, dd, 2J = 3.0, 3J = 5.4, H-2);
2.71-2.88 (3H, m, aliph.); 4.68-4.82 (1H, m, OCH);
4.53–5.52 (1H, br. s, ОH); 6.55 (1H, d,
J
J
= 2.4,
o
-H arom.); 6.61 (1H, dd,
J
= 2.4,
= 8.3, o-H arom.); 7.14 (1H, d,
J
= 8.3, m-H arom.)
2h
H
3-Methoxy- 0.86 (3H, s, CH3); 1.05 (1H, br. s, NH);
estradiolyl
1.17-2.08 (12H, m, aliph.); 2.12-2.38 (3H, m, aliph.);
2.47-2.59 (1H, m, aliph.); 2.79-2.93 (2H, m, aliph.);
3.78 (3H, s, OCH3); 4.69-4.84 (1H, m, OCH);
6.63 (1H, d,
J
= 2.8,
o
-H arom.);
6.71 (1H, dd,
J
= 2.8,
J = 8.6, o-H arom.);
7.20 (1H, d,
1.47 (9H, s,
J
= 8.6, m-H arom.)
4a
4b
4c
СН2ОMе
t-Bu
t-Bu
t
-Bu); 1.81 (1H, dd, 2J = 1.2, 3Jcis = 6.8,
cis-H-3); 2.07 (1H, dd, 2J = 1.2, 3Jtrans = 3.0,
trans-H-3); 2.27 (1H, dd, 3Jtrans = 3.0, 3Jcis = 6.8, H-2);
3.43 (3H, s, OCH3); 3.93 and 3.97 (1H and 1H,
АB system, J = 7.9, NCH2O)
Bn
1.46 (9H, s, t-Bu); 1.64 (1H, unresolved dd,
3Jcis = 6.3, cis-H-3); 2.07 (1H, dd, 3Jtrans = 3.2,
3Jcis = 6.3, H-2); 2.19 (1H, dd, 2J = 1.3, 3Jtrans = 3.2,
trans-H-3); 3.54 and 3.57 (1H and 1H, АB system,
J
= 13.7, CH2Ph); 7.19-7.38 (5H, m, arom.)
Bn
Bn
Menthyl
Menthyl
t-Bu
0.60-2.27 (21H, m, aliph.);
3.37 and 3.73 (1H and 1H, АM system, J = 13.8,
CH2Ph); 4.73 (1H, dt, 3J = 4.4, 3J = 10.7, OCH);
7.11-7.40 (5H, m, arom.)
4'c
4d
0.46-2.33 (21H, m, aliph.);
3.26 and 3.85 (1H and 1H, АM system, J = 13.7,
CH2Ph); 4.75 (1H, dt, 3J = 4.4, 3J = 10.9, OCH);
7.04-7.48 (5H, m, arom.)
CPh3
1.31 (1H, dd, 2J = 1.6, 3Jcis = 6.1, cis-H-3);
1.49 (9H, s, t
-Bu); 1.77 (1H, dd, 3Jtrans = 2.6,
3Jcis = 6.1, H-2); 2.20 (1H, dd, 2J = 1.6,
3Jtrans = 2.6, trans-H-3); 7.16-7.34 (9H, m, arom.);
7.46-7.56 (6H, m, arom.)
4e
CO2Bn
CO2Bn
CO2Bn
Bn
2.47 (1H, dd, 2J = 1.2, 3Jcis = 5.6, cis-H-3);
2.62 (1H, dd, 2J = 1.2, 3Jtrans = 3.1, trans-H-3);
3.14 (1H, d.d, 3Jtrans = 3.1, 3Jcis = 5.6, H-2);
5.02-5.21 (4H, m, CH2Ph);
7.32-7.38 (10H, m, arom.)
R
R
,
S
-4f
t-Bu
t-Bu
1.45 (9H, s, t
-Bu); 2.40 (1H, dd, 2J = 1.3, 3Jcis = 5.0,
cis-H-3); 2.55 (1H, dd, 2J = 1.3, 3Jtrans = 3.1,
trans-H-3); 3.00 (1H, dd, 3Jtrans = 3.1, 3Jcis = 5.0, H-2);
5.11 and 5.17 (1H and 1H, АB system, J = 12.1,
CH2Ph); 7.32-7.40 (5H, m, arom.)
-4f
1.45 (9H, s, t
-Bu); 2.40 (1H, dd, 2J = 1.3, 3Jcis = 5.0,
cis-H-3); 2.55 (1H, dd, 2J = 1.3, 3Jtrans = 3.1,
trans-H-3); 3.00 (1H, dd, 3Jtrans = 3.1, 3Jcis = 5.0, H-2);
5.11 and 5.17 (1H and 1H, АB system,
J
= 12.1, CH2Ph); 7.32-7.40 (5H, m, arom.)
730

TABLE 3 (continued)
1
2
3
4
4g
COOBu-t
Bn
1.43 (9H, s, t-Bu); 2.40 (1H, dd, 2J = 1.4, 3Jcis = 5.2,
cis-H-3); 2.55 (1H, dd, 2J = 1.2, 3Jtrans = 3.3,
trans-H-3); 3.00 (1H, dd, 3Jtrans = 3.2, 3Jcis = 5.1, H-2);
5.18 and 5.25 (1H and 1H, АB system,
J = 12.4, CH2Ph); 7.30-7.42 (5H, m, arom.)
4h
4i
COOBu-t
COOBu-t
t-Bu
1.47 (9H, s, t-Bu); 1.50 (9H, s, t-Bu); 2.32 (1H, dd,
2J = 1.6, 3Jcis = 5.2, cis-H-3); 2.47 (1H, dd, 2J = 1.6,
3Jtrans = 3.1, trans-H-3); 2.93 (1H, dd, 3Jtrans = 3.1,
3Jcis = 5.2, H-2)
Nonyl
0.86 (3H, t, J = 6.7, nonyl CH3);
1.16-1.49 (21H, m, nonyl, t-Bu);
1.55-1.73 (2H, m, aliph.); 2.38 (1H, dd, 2J = 1.5,
3Jcis = 5.5, cis-H-3); 2.50 (1H, dd, 2J = 1.5,
3Jtrans = 3.2, trans-H-3); 3.00 (1H, dd, 3Jtrans = 3.2,
3Jcis = 5.5, H-2); 4.02-4.26 (2H, m, OCH2)
4j
CONMe2
Bn
2.48 (1H, dd, 2J = 1.2, 3Jtrans = 3.2, trans-H-3);
2.55 (1H, dd, 2J = 1.2, 3Jcis = 6.3, cis-H-3);
2.92 (3H, s, CH3); 3.02-3.08 (1H, unresolved dd,
H-2); 3.05 (3H, s, CH3); 5.14-5.28 (2H, m, CH2Ph);
7.34-7.39 (5H, m, arom.)
4m
4n
CH(Ph)CH2OMe
t-Bu
1.42 (1H, dd, 2J = 1.0, 3Jcis = 6.3, cis-H-3);
1.50 (9H, s, t-Bu ); 2.01 (1H, dd, 2J = 1.0,
3Jtrans = 3.4, trans-H-3); 2.38 (1H, dd, 3Jtrans = 3.4,
3Jcis = 6.3, H-2); 2.69 (1H, dd, J = 4.8, J = 7.7, NCH);
3.37 (3H, s, OCH3); 3.61 (1H, dd, J = 4.8,
J = 9.8, OCH); 3.70 (1H, dd, J = 7.7, J = 9.8, OCH);
7.25-7.45 (5H, m, arom.)
CH(Ph)CH2OMe
t-Bu
1.40 (9H, s, t-Bu), 1.87 (1H, dd, 3Jtrans = 3.3,
3Jcis = 6.4, H-2); 1.98 (1H, dd, 2J = 1.0,
3Jcis = 6.3, cis-H-3); 2.39 (1H, dd, 2J = 1.0,
3Jtrans = 3.3, trans-H-3); 2.75 (1H, dd, J = 4.5, J = 7.9,
NCH); 3.34 (3H, s, OCH3); 3.54 (1H, dd,
J = 4.8, J = 9.8, OCH); 3.72 (1H, dd, J = 7.9,
J = 9.8, OCH); 7.23-7.42 (5H, m, arom.)
We have shown by two different methods B and C (using potassium tert-butylate as base) that
transesterification of the diastereomeric esters 4k and 4l proceeds with retention of the configuration of the
substituent at the aziridine nitrogen atom and have obtained the corresponding diastereomeric esters 4m and 4n.
O
O
(S)
N
B: t-BuOH, n-BuLi, THF, -20°C – room temp.
C: t-BuOK, THF, -20°C – room temp.
OMe
OBu-t
OMe
N
OMe
Ph
Ph
70% (B)
82% (C)
H
H
4k
4m
O
O
(R)
N
B: t-BuOH, n-BuLi, THF, -20°C – room temp.
C: t-BuOK, THF, -20°C – room temp.
OMe
OBu-t
OMe
N
OMe
29% (B)
74% (C)
Ph
Ph
H
H
4n
4l
731

TABLE 4. Physicochemical Characteristics of Esters of Aziridine-2-
carboxylic Acids 2 and 4
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
Rf *
mp, °С
C
H
N
2b
2d
2e
C10H10N2O4
C13H19NO2
C13H23NO2
C21H27NO3
C22H29NO3
C20H29NO2
C20H29NO2
C26H27NO2
C15H19NO4
C12H21NO4
C16H23NO3
C16H23NO3
52.69
54.06
69.30
70.56
68.38
69.29
73.63
73.87
74.14
74.33
75.44
76.15
76.00
76.15
80.89
81.01
64.94
64.97
59.05
59.24
69.30
69.29
69.11
69.29
4.64
4.54
8.59
8.65
10.13
10.29
8.24
7.97
8.28
8.22
9.60
9.27
9.23
9.27
7.05
7.06
6.89
6.91
8.79
8.70
8.40
8.36
8.51
8.36
12.16
12.61
6.28
6.33
5.65
6.22
3.50
4.10
3.92
3.94
3.97
4.44
4.36
4.44
3.65
3.63
5.11
5.05
5.57
5.76
4.99
5.05
5.03
5.05
0.13
0.58
0.62
0.26
0.15
0.63
0.57
0.36
0.57
0.77
0.59
0.46
115-117
2g
2h
4c
129-130
135-136
107-109
4'c
4d
4f
111-112
146-147
137.5-138.5
4h
4m
4n
128
_______
* Mobile phase in TLC: ethyl acetate–petroleum ether, 1:1 (compounds
2b,d,e,g, 4c, 4'c, 4m,n), 1:3 (compounds 2h, 4f), 1:9 (compounds 4d,h).
EXPERIMENTAL
The 1H NMR spectra were recorded on a Varian Mercury 200 (200 MHz) spectrometer, internal standard
was TMS. Elemental analyses were carried out on a Carlo Erba EA 1108 apparatus. Melting points were
determined on a Gallenkamp heating stage and are not corrected. TLC was carried out on DC Alufolien plates of
Kieselgel 60. Chiral HPLC of compounds 4f and 4f-l was carried out on a Gilson chromatographic system and a
column of Chiralcel OD (Daicel), in hexane—ethanol, 95 : 5 (flow rate 1.0 ml/min and UV detector at 254 nm).
Dry THF was prepared by double distillation over sodium (second time in the presence of benzoquinone).
Transesterification of Aziridine-2-carboxylic Acid Methyl Ester and Its Derivatives (General
Procedure). A. Compounds 2a-h (Tables 1,3,4). Potassium carbonate (41.4 g, 300 mmol) was added with
stirring to a solution of aziridine-2-carboxylic acid methyl ester [1] (10.1 g, 100 mmol) in the alcohol
(100 mmol) at ~20°C. The mixture obtained was stirred and heated at 150°C in a stream of argon while distilling
off the methanol. The reaction mixture was then cooled to room temperature, poured into water (50 ml), and
extracted with ether (3 × 20 ml). The combined ether extracts were washed with water (2 × 20 ml), and with
saturated NaCl solution (20 ml), then dried over Na2SO4, the solution filtered, and the solvent evaporated in
vacuum. The obtained esters were purified by chromatography on silica gel with petroleum ether–ethyl acetate,
or by distillation in vacuum.
732

B. Compounds 2a-h and 4a-j (Tables 1-4). A round-bottomed flask (100 ml) was placed in a heater for
5 h at 150°C and cooled in a stream of argon to room temperature. The alcohol (100 mmol) was placed in the
flask and absolute THF (10 ml) was added. The obtained solution was cooled to -20°C in a stream of argon and
BuLi (40 ml, 100 mmol) was added dropwise as a 2.5 M solution in hexane. The solution of alcoholate obtained
was stirred at -20°C for 15 min, a solution of aziridine-2-carboxylic acid methyl ester (100 mmol) in absolute
THF (15 ml) was added, the mixture was stirred for 1-5 h at -20°C, heated to room temperature, poured into ice
water (20 ml), and extracted with ether (3 × 20 ml). The ether extracts were combined, washed with water
(2 × 20 ml), and with saturated NaCl solution (20 ml), dried over Na2SO4, and the solvent evaporated in vacuum.
The esters obtained were purified by chromatography on silica gel in the system petroleum ether–ethyl acetate,
or by distillation in vacuum.
C. Compounds 4m and 4n (Tables 3, 4). A round-bottomed flask (100 ml) was placed in a heater at
150°C for 5 h and cooled in a current of argon to room temperature. Potassium tert-butylate (100 mmol) was
placed in the flask and absolute THF (15 ml) was added. The solution obtained was cooled in a current of argon
to -20°C and a solution of aziridine-2-carboxylic acid methyl ester (100 mmol) in absolute THF (15 ml) was
added dropwise. The mixture was stirred at -20°C for 1.5 h, heated to room temperature, poured into ice water
(25 ml), and extracted with ether (3 × 25 ml). The ether extracts were combined, washed with water (2 × 25 ml),
and with saturated NaCl solution (25 ml), dried over Na2SO4, and evaporated. The esters obtained were purified
by chromatography on silica gel in the system petroleum ether–ethyl acetate, 4:1.
The work was carried out with the financial support of the Latvian Council for Science (grant LZP
01.192).
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