Azacycloalkanes: XXXIX. New Syntheses of 1H-Pyrrole-1-carboxylic acid and 1,2-dihydropyrrolo-[1,2-a]pyrazin-3(4H)-one derivatives

Article abstract of DOI:10.1134/S1070428009120136

New procedures have been developed for the synthesis of α-(2-formyl-1H-pyrrol-1-yl)-substituted carboxylic acids, α-(2-R-aminomethyl-1H-pyrrol-1-yl)-substituted carboxylic acids, and 1,2-dihydropyrrolo-[1,2-a]pyrazin-3(4H)-ones on the basis of furfurol and α-amino acids.

Full text of DOI:10.1134/S1070428009120136

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 12, pp. 1829–1833. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © G.V. Mokrov, A.M. Likhosherstov, V.S. Troitskaya, T.A. Gudasheva, 2009, published in Zhurnal Organicheskoi Khimii, 2009,
Vol. 45, No. 12, pp. 1832–1836.
Azacycloalkanes: XXXIX.* New Syntheses
of 1H-Pyrrole-1-carboxylic Acid and 1,2-Dihydropyrrolo-
[1,2-a]pyrazin-3(4H)-one Derivatives
G. V. Mokrov, A. M. Likhosherstov, V. S. Troitskaya, and T. A. Gudasheva
Zakusov Research Institute of Pharmacology, Russian Academy of Medical Sciences,
ul. Baltiiskaya 8, Moscow, 125315 Russia
e-mail: g.mokrov@gmail.com
Received December 4, 2008
Abstract—New procedures have been developed for the synthesis of α-(2-formyl-1H-pyrrol-1-yl)-substituted
carboxylic acids, α-(2-R-aminomethyl-1H-pyrrol-1-yl)-substituted carboxylic acids, and 1,2-dihydropyrrolo-
[1,2-a]pyrazin-3(4H)-ones on the basis of furfurol and α-amino acids.
DOI: 10.1134/S1070428009120136
We previously described methods for the synthesis
of a series of 1,2-substituted pyrroles [2] and 3,4-dihy-
dropyrrolo[1,2-a]pyrazines [3, 4] and showed that
some of these compounds exhibit cardiovascular [2]
and psychotropic [5] activity. It is also known that the
process of preparing food by heating is accompanied
by formation of various pyrrole and pyrrolo[1,2-a]pyr-
azine derivatives from carbohydrates and proteins
[6, 7], and these compounds are introduced into human
organism together with food. Therefore, target-oriented
syntheses of such compounds are very important from
the viewpoints of both search for new medical agents
and elucidation of their biological effect in the nutri-
tion process.
amount of water depended on the solubility of the
initial amino acid. The results of the reactions with
optically active (R)- and (S)-α-alanines and racemic
(RS)-α-alanine demonstrated that the proposed proce-
dure can be successfully used for the preparation of
individual stereoisomers. Acids IIIb and IIIc were
characterized by similar (in absolute value) but op-
posite in sign specific rotations and similar melting
points (mp 131–132°C), while racemic compound IIId
melted at 110–112°C. Furthermore, a mixture of equal
amounts of the (S)-isomer and (RS)-compound showed
depression of the melting point (mp 107–108°C). The
above data indicated that no racemization occurred
during the synthesis of acids III.
In order to elucidate the mechanism of formation of
acids III, we examined the reaction of glycine (IIa)
with 2-oxopentanedial (A) which was obtained by hy-
drolysis of acetal I with dilute hydrochloric acid. This
reaction afforded only traces of acid IIIa, indicating
that the condensation of glycine with tricarbonyl
system A involves terminal carbonyl groups in the
latter rather than those in the 1,4-positions. Presum-
ably, the reaction of acetal I with amino acids II begins
with hydrolysis of the least stable endocyclic ketal
moiety in molecule I. Next follows condensation of the
amino acid at the ketone carbonyl group, and the sub-
sequent reaction at the emerging aldehyde group in
position 5 closes five-membered nitrogen-containing
heteroring. Aromatization via elimination of water and
methanol and simultaneous hydrolysis of the dime-
In the present communication we report on new
methods of synthesis of α-(2-formyl-1H-pyrrol-1-yl)-
substituted carboxylic acids III, α-(2-R-aminomethyl-
1H-pyrrol-1-yl)-substituted carboxylic acids IV, and
pyrrolo[1,2-a]pyrazine derivatives V and VI from
2,5-dimethoxy-2-(dimethoxymethyl)tetrahydrofuran
(I) and α-amino acids II. Acetal I is readily prepared
from accessible 2-furaldehyde [8]; it reacted with
amino acids IIa–IIf to give the corresponding
2-(2-formyl-1H-pyrrol-1-yl)alkanoic acids IIIa–IIIf in
high yield (Scheme 1). The optimal reaction conditions
implied heating the reactants at a I-to-II molar ratio of
1.1:1 in boiling water over a period of 1 h; these con-
ditions ensured 80–90% yield of acids IIIa–IIIf. The
* For communication XXVIII, see [1].
1829

MOKROV et al.
1830
Scheme 1.
NH2
OMe
OMe
*
OH
MeO
CHO
+
R1
N
*
O
OMe
R1
COOH
I
IIa–IIf
IIIa–IIIf
H
N
N
R2NH2
H2, Pd/C
R2
R2
N
N
*
*
R1
COOH
R1
COOH
B
IVa–IVf
O
H2O, H+
H2NCH2COOH (IIa)
I
IIIa (traces)
OCH
CHO
A
III, R1 = H (a), Me (R) (b), Me (S) (c), Me (RS) (d), Et (RS) (e), PhCH2 (RS) (f); IV, R1 = H, R2 = Me (a), i-Bu (b), PhCH2 (c),
3,4-(MeO)2C6H3CH2 (d); R1 = Me, R2 = PhCH2 (e), 3,4-(MeO)2C6H3CH2 (f).
thoxymethyl group in position 2 to aldehyde yield the
final product.
the corresponding methyl esters D, whereas acids IVa–
IVd themselves failed to undergo cyclization in dif-
ferent solvents or on heating. Amino acids IVa–IVd
were treated with thionyl chloride in methanol at –5 to
–10°C to obtain amino ester hydrochlorides C which
were converted into free amino esters by the action of
alkali in water. The rate of lactamization of esters D
depended on the nature of the R2 substituent. Com-
pound Va (R2 = Me) was formed during the isolation
procedure and subsequent vacuum distillation. N-Iso-
butyl derivative Vb required heating for 3 h in boiling
toluene, whereas benzylamino compounds Vc and Vd
were formed during workup. Compounds Va–Vd were
isolated as crystalline or oily substances.
A particular problem was to develop a procedure
for the synthesis of 1,2-dihydropyrrolo[1,2-a]pyrazin-
3(4H)-one (VI). This compound was obtained from
acid IIIa as shown in Scheme 3 through intermediate
(2-aminomethyl-1H-pyrrol-1-yl)acetic acid E. The lat-
ter was prepared by reductive amination of acid IIIa,
which was performed in two ways. The first of these
(method b) was reported previously [11]. It implied
Acids IIIa–IIIf were isolated as reddish crystalline
substances. Some analogous compounds have already
been reported [6, 9, 10], but the procedure proposed by
us is more advantageous due to its general character,
experimental simplicity (one step), high yields, and the
use of accessible starting compounds.
By hydrogenation of mixtures of acids III with
primary amines at a molar ratio of 1:1.1 in methanol
or aqueous methanol over 10% Pd/C under atmos-
pheric pressure we obtained amino acids IVa–IVf.
Presumably, the corresponding Schiff bases B were
formed as intermediates. Amino acids IVa–IVf were
isolated as colorless or slightly colored high-melting
crystalline substances.
We tried to effect intramolecular cyclization of
(2-R-aminomethyl-1H-pyrrol-1-yl)acetic acids IVa–
IVd with a view to obtain 1,2-dihydropyrrolo[1,2-a]-
pyrazin-3(4H)-one derivatives Va–Vd (Scheme 2). We
found that such cyclization was successful only with
Scheme 2.
H
N
H
R2
N
R2
R2
MeOH, SOCl2
OH–
N
IVa–IVd
N
·HCl
N
N
O
COOMe
COOMe
C
D
Va–Vd
R2 = Me (a), i-Bu (b), PhCH2 (c), 3,4-(MeO)2C6H3CH2 (d).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

AZACYCLOALKANES: XXXIX.
1831
Scheme 3.
NH2OH, H2, Pd/C (a)
or NaB(CN)H3, NH4OAc (b)
NH2
NH2
OH–
HN
MeOH, SOCl2
IIIa
N
N
·HCl
N
O
COOH
COOMe
E
F
VI
reductive amination of acid IIIa with ammonium ace-
tate and sodium cyanotrihydridoborate. The resulting
mixture was subjected to esterification and lactamiza-
tion as described above for amino acids IV. In such
a way we isolated compound VI in ~12% yield calcu-
lated on the initial acid IIIa. The second procedure
(method a) was developed by us and was more effec-
tive. A mixture of acid IIIa with hydroxylamine in
methanol was hydrogenated over 10% Pd/C under at-
mospheric pressure, and the subsequent esterification
and lactamization gave ~32% of compound VI.
(2R)-2-(2-Formyl-1H-pyrrol-1-yl)propionic acid
(IIIb). Yield 7.11 g (85%), red–orange crystals,
mp 131–132°C (from H2O), [α]D20 = +72.5° (c = 0.2,
1
ethanol). H NMR spectrum (DMSO-d6), δ, ppm:
1.69 d (3H, Me), 5.16 q (1H, CH), 6.27 m (1H, 3-H),
7.07 m (1H, 4-H), 7.40 m (1H, 5-H), 9.47 s (1H,
CHO). Found, %: C 57.65; H 5.61; N 8.51. C8H9NO3.
Calculated, %: C 57.48; H 5.43; N 8.38.
(2S)-2-(2-Formyl-1H-pyrrol-1-yl)propionic acid
(IIIc). Yield 7.11 g (85%), red–orange crystals,
mp 131–132°C (from H2O), [α]D20 = –72.5° (с = 0.2,
1
To conclude, we have developed new procedures
for the synthesis of α-(2-formyl-1H-pyrrol-1-yl)- and
α-(2-R-aminomethyl-1H-pyrrol-1-yl)-substituted car-
boxylic acids and 1,2-dihydropyrrolo[1,2-a]pyrazin-
3(4H)-ones. The structure of the isolated compounds
ethanol). The H NMR spectrum was identical to that
of IIIb. Found, %: C 57.27; H 5.55; N 8.53. C8H9NO3.
Calculated, %: C 57.48; H 5.43; N 8.38.
(2RS)-2-(2-Formyl-1H-pyrrol-1-yl)propionic
acid (IIId). Yield 6.86 g (82%), red–orange crystals,
1
was confirmed by the H NMR spectra and elemental
1
mp 110–112°C (from H2O). The H NMR spectrum
analyses.
was identical to that of IIIb. Found, %: C 57.46;
H 5.60; N 8.49. C8H9NO3. Calculated, %: C 57.48;
H 5.43; N 8.38.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
(2RS)-2-(2-Formyl-1H-pyrrol-1-yl)butanoic acid
(IIIe). Yield 7.42 g (82%), light brown crystals,
AC-250 spectrometer using tetramethylsilane as inter-
nal reference. Thin-layer chromatography was per-
formed on Kieselgel 60 F254 plates (Merck); detection
under UV light; eluent toluene–acetone–heptane–tri-
ethylamine (14:9:3:1).
1
mp 94–95°C (from H2O). H NMR spectrum
(DMSO-d6), δ, ppm: 0.69 t (3H, Me), 2.06 m (2H,
CH2), 5.55 t (1H, CH), 6.26 m (1H, 3-H), 7.06 m (1H,
4-H), 7.42 m (1H, 5-H), 9.47 s (1H, CHO). Found, %:
C 59.53; H 6.08; N 7.72. C9H11NO3. Calculated, %:
C 59.66; H 6.12; N 7.73.
2-(2-Formyl-1H-pyrrol-1-yl)alkanoic acids IIIa–
IIIf (general procedure). A solution of 50 mmol of
amino acid IIa–IIe in 60 ml of water (or acid IIf in
240 ml of water) and 11.32 g (55 mmol) of 2,5-di-
methoxy-2-(dimethoxymethyl)tetrahydrofuran (I) was
heated for 1 h under reflux. The mixture was evapo-
rated by half and cooled to room temperature, and the
precipitate was filtered off, washed with water, and
dried.
(2RS)-2-(2-Formyl-1H-pyrrol-1-yl)-3-phenylpro-
pionic acid (IIIf). Yield 10.70 g (88%), light brown
1
crystals, mp 129–130°C (from H2O). H NMR spec-
trum (DMSO-d6), δ, ppm: 3.40 d.d.d (2H, CH2),
5.93 m (1H, CH), 6.15 m (1H, 3-H), 6.95 m (1H, 4-H),
7.00–7.12 m (5H, Harom), 7.31 m (1H, 5-H), 9.35 s
(1H, CHO). Found, %: C 69.20; H 5.38; N 5.71.
C14H13NO3. Calculated, %: C 69.12; H 5.39; N 5.76.
(2-Formyl-1H-pyrrol-1-yl)acetic acid (IIIa).
Yield 6.90 g (90%), orange crystals, mp 140–141°C
(from H2O); published data [9]: mp 141–143°C.
1H NMR spectrum (DMSO), δ, ppm: 4.98 s (2H, CH2),
6.23 m (1H, 3-H), 7.06 m (1H, 4-H), 7.26 m (1H, 5-H),
9.45 s (1H, CHO). Found, %: C 54.81; H 4.50; N 9.02.
C7H7NO3. Calculated, %: C 54.90; H 4.60; N 9.15.
N-Substituted 2-(2-aminomethyl-1H-pyrrol-1-
yl)alkanoic acids IVa–IVf (general procedure). A so-
lution of 30 mmol of acid IIIa–IIIf and 33 mmol of
the corresponding primary amine in 100 ml of meth-
anol was kept for 1 h, 0.4 g of 10% Pd/C was added,
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MOKROV et al.
1832
and hydrogen was supplied under atmospheric pressure
until its required amount was absorbed. The catalyst
was filtered off, the filtrate was evaporated to 1/4 of
the initial volume, and the precipitate was filtered off,
washed with methanol, and dried.
7.17–7.41 m (5H, Ph). Found, %: C 69.51; H 6.88;
N 10.96. C15H18N2O2. Calculated, %: C 69.74; H 7.02;
N 10.84.
2-{2-[(3,4-Dimethoxybenzyl)aminomethyl]-1H-
pyrrol-1-yl)propionic acid (IVf). Yield 7.35 g (77%),
white powder, mp 159–160°C (from MeOH). 1H NMR
spectrum (DMSO-d6), δ, ppm: 1.48 d (3H, Me), 3.70 s
(6H, OMe), 3.93 s (2H, NHCH2), 4.20 s (2H, 2-CH2),
4.56 q (1H, 1-CH), 6.00 m (1H, 3-H), 6.14 m (1H,
4-H), 6.81 m (1H, 5-H), 6.90–7.10 m (3H, Harom).
Found, %: C 64.40; H 7.17; N 9.00. C17H22N2O4. Cal-
culated, %: C 64.13; H 6.97; N 8.80.
2-[2-(Methylaminomethyl)-1H-pyrrol-1-yl]acetic
acid (IVa) was synthesized by reductive amination of
acid IIIa in aqueous methanol (100 ml of methanol
and 30 ml of water), followed by evaporation to dry-
ness and purification by heating in boiling methanol.
Yield 3.74 g (74%), white powder, mp 206–207°C
(from MeOH). 1H NMR spectrum (DMSO-d6), δ, ppm:
2.52 s (3H, Me), 4.03 s (2H, CH2NH), 4.72 s (2H,
1-CH2), 6.02 m (1H, 3-H), 6.25 m (1H, 4-H), 6.64 m
(1H, 5-H). Found, %: C 57.03; H 7.27; N 16.44.
C8H12N2O2. Calculated, %: C 57.13; H 7.19; N 16.67.
2-Methyl-1,2-dihydropyrrolo[1,2-a]pyrazin-
3(4H)-one (Va). A suspension of 4.49 g (26.7 mmol)
of amino acid IVa in 50 ml of methanol was cooled to
–10 to –5°C, 2.87 ml (39.8 mmol) of thionyl chloride
was added dropwise under stirring, and the mixture
was kept for 24 h. The mixture was evaporated to
dryness, and the residue was treated with a 10% aque-
ous solution of potassium carbonate until pH 11. The
product was extracted into toluene, and the extract was
washed with water, filtered through a filter paper, and
evaporated to dryness. The residue was distilled under
reduced pressure. Yield 2.89 g (72%), colorless crys-
tallizable oily substance, bp 103–104°C (1.5 mm),
2-[2-(Isobutylaminomethyl)-1H-pyrrol-1-yl]-
acetic acid (IVb). Yield 4.35 g (69%), white powder,
1
mp 185–186°C (from MeOH). H NMR spectrum
(DMSO-d6), δ, ppm: 0.93 d (6H, Me), 1.86 m (1H,
NHCH2CH), 2.64 d (2H, NHCH2CH), 4.04 s (2H,
2-CH2), 4.70 s (2H, 1-CH2), 5.95 m (1H, 3-H), 6.13 m
(1H, 4-H), 6.78 m (1H, 5-H). Found, %: C 62.96;
H 8.54; N 13.21. C11H18N2O2. Calculated, %: C 62.83;
H 8.63; N 13.32.
1
mp 54–56°C. H NMR spectrum (CDCl3), δ, ppm:
2-[2-(Benzylaminomethyl)-1H-pyrrol-1-yl]acetic
acid (IVc). Yield 5.64 g (77%), white powder,
3.09 s (3H, Me), 4.50 s (2H, 1-H), 4.57 s (2H, 4-H),
5.95 m (1H, 8-H), 6.20 m (1H, 7-H), 6.57 m (1H, 6-H).
Found, %: C 63.58; H 6.78; N 18.58. C8H10N2O. Cal-
culated, %: C 63.98; H 6.71; N 18.65.
1
mp 175–177°C (from MeOH). H NMR spectrum
(CDCl3), δ, ppm: 2.60 br.s (1H, NH), 3.78 s (2H,
CH2Ph), 3.85 s (2H, 2-CH2), 4.07 s (2H, 1-CH2),
6.06 m (1H, 3-H), 6.21 m (1H, 4-H), 6.67 m (1H, 5-H),
7.21–7.47 m (5H, Ph). Found, %: C 68.47; H 6.80;
N 11.64. C14H16N2O2. Calculated, %: C 68.83; H 6.60;
N 11.47.
2-Isobutyl-1,2-dihydropyrrolo[1,2-a]pyrazin-
3(4H)-one (Vb) was synthesized in a similar way from
amino acid IVb. The toluene extract containing ester D
(R2 = i-Bu) was additionally heated for 3 h under
reflux and evaporated to dryness, and the residue was
distilled under reduced pressure. Yield 3.49 g (68%),
colorless oily substance, bp 120–122°C (1.5 mm),
[α]D20 = 1.5292. 1H NMR spectrum (DMSO-d6), δ, ppm:
0.74 d (6H, Me), 1.77 m (1H, CH), 3.25 d (2H,
NCH2CH), 4.50 s (2H, 1-H), 4.60 s (2H, 4-H), 5.72 m
(1H, 8-H), 6.05 m (1H, 7-H), 6.74 m (1H, 6-H).
Found, %: C 68.35; H 8.32; N 14.79. C11H16N2O4. Cal-
culated, %: C 68.72; H 8.39; N 14.57.
2-{2-[(3,4-Dimethoxybenzyl)aminomethyl]-1H-
pyrrol-1-yl)acetic acid (IVd). Yield 7.21 g (79%),
white powder, mp 191–193°C (from MeOH). 1H NMR
spectrum (CDCl3), δ, ppm: 2.63 br.s (1H, NH), 3.81 s
(6H, OMe), 3.87 s (2H, NHCH2), 3.93 s (2H, 2-CH2),
4.45 s (2H, 1-CH2), 6.12 m (1H, 3-H), 6.24 m (1H,
4-H), 6.70 m (1H, 5-H), 6.75–7.07 m (3H, Harom).
Found, %: C 62.86; H 6.78; N 9.33. C16H20N2O4. Cal-
culated, %: C 63.14; H 6.62; N 9.20.
2-Arylmethyl-1,2-dihydropyrrolo[1,2-a]pyrazin-
3(4H)-ones Vc and Vd (general procedure). A sus-
pension of 26.7 mmol of benzylamino acid IVc or IVd
in 50 ml of methanol was cooled to –10 to –5°C, and
2.87 ml (39.8 mmol) of thionyl chloride was added
dropwise under stirring. After 24 h, the mixture was
evaporated to dryness, and the residue was treated with
2-[2-(Benzylaminomethyl)-1H-pyrrol-1-yl]pro-
pionic acid (IVe). Yield 6.74 g (87%), light yellow
powder, mp 151–152°C (from MeOH). 1H NMR spec-
trum (DMSO-d6), δ, ppm: 1.64 d (3H, Me), 4.15 s (2H,
CH2Ph), 4.25 s (2H, 2-CH2), 4.93 q (1H, 1-CH),
6.15 m (1H, 3-H), 6.35 m (1H, 4-H), 6.88 m (1H, 5-H),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

AZACYCLOALKANES: XXXIX.
1833
a 10% aqueous solution of potassium carbonate to pH
11 and extracted with toluene. The extract was washed
with water, passed through a column charged with
aluminum oxide, and evaporated to dryness. The resi-
due was recrystallized from ethanol.
(1H, 6-H), 7.32 s (1H, NH). Found, %: C 61.85;
H 6.03; N 20.47. C7H8N2O. Calculated, %: C 61.75;
H 5.92; N 20.57.
b. (2-Formyl-1H-pyrrol-1-yl)acetic acid (IIIa),
4.59 g (30 mmol), and ammonium acetate, 18.5 g
(240 mmol), were dissolved in 75 ml of methanol,
3.0 g (48 mmol) of sodium cyanotrihydridoborate was
added, and the mixture was kept for 48 h and evapo-
rated to dryness. The residue was acidified with
3% hydrochloric acid to pH 2 and evaporated to dry-
ness, 100 ml of methanol was added to the residue, the
resulting suspension was cooled to –10 to –5°C, and
3.1 ml (43 mmol) of thionyl chloride was added drop-
wise under stirring. The mixture was then treated as
described above in a. Yield 0.49 g (12%). The melting
2-Benzyl-1,2-dihydropyrrolo[1,2-a]pyrazin-
3(4H)-one (Vc). Yield 5.01 g (83%), yellow crystals,
1
mp 78–80°C (from EtOH). H NMR spectrum
(DMSO-d6), δ, ppm: 4.43 s (2H, CH2Ph), 4.66 s (2H,
1-H), 4.72 s (2H, 4-H), 5.85 m (1H, 8-H), 6.06 m (1H,
7-H), 6.72 m (1H, 6-H), 7.25–7.40 m (5H, Ph). Found,
%: C 74.25; H 6.35; N 12.40. C14H14N2O. Calculated,
%: C 74.31; H 6.24; N 12.38.
2-(3,4-Dimethoxybenzyl)-1,2-dihydropyrrolo-
[1,2-a]pyrazin-3(4H)-one (Vd). Yield 5.20 g (68%),
colorless crystals, mp 96–97°C (from EtOH). 1H NMR
spectrum (DMSO-d6), δ, ppm: 3.72 s (6H, OMe),
4.41 s (2H, 2-CH2), 4.58 s (2H, 1-H), 4.70 s (2H, 4-H),
5.84 m (1H, 8-H), 6.04 m (1H, 7-H), 6.70 m (1H, 6-H),
6.77–6.92 m (3H, Harom). Found, %: C 67.15;
H 6.43; N 10.05. C16H18N2O3. Calculated, %: C 67.12;
H 6.34; N 9.78.
1
point and H NMR spectrum of the product were
identical to those of a sample obtained as described
above in a.
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Schindler, R., Heterocycles, 2008, vol. 75, p. 2713.
1,2-Dihydropyrrolo[1,2-a]pyrazin-3(4H)-one
(VI). a. A solution of 7.7 g (50 mmol) of (2-formyl-
1H-pyrrol-1-yl)acetic acid (IIIa) and 8.3 g (55 mmol)
of 50% aqueous hydroxylamine in a mixture of 100 ml
of methanol and 30 ml of water was kept for 1 h, 1 g of
10% Pd/C was added, and hydrogen was supplied until
its required amount was absorbed. The catalyst was
filtered off, the filtrate was evaporated to dryness,
100 ml of methanol was added to the residue, the
resulting suspension was cooled to –10 to –5°C, and
4.6 ml (63 mmol) of thionyl chloride was added drop-
wise under stirring. After 24 h, the solution was
evaporated to dryness, and the residue was treated with
a 10% aqueous solution of potassium carbonate to
pH 11 and extracted with chloroform. The extract was
washed with water and evaporated, and the residue
was subjected to column chromatography on alumi-
num oxide using chloroform as eluent. Chromato-
graphically similar fractions (Rf 0.38) were combined
and evaporated to dryness, and the residue was recrys-
tallized from ethanol. Yield 2.18 g (32%), light yellow
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