Practical synthetic approach to 4-acetoxy-2-azetidinone for the preparation of carbapenem and penem antibiotics

Article abstract of DOI:10.1007/s11164-011-0344-5

A practical synthesis of 4-acetoxy-2-azetidinone useful for the preparation of carbapenem- and penem-type antibiotics is described. The synthesis has advantages such as avoiding the tedious and costly column chromatographic or recrystallized separation steps for diastereomers. The overall yield of the product is greatly improved and the process is also more economical for large-scale production. In addition, the mechanism for oxidative decarboxylation is also present. Springer Science+Business Media B.V. 2011.

Full text of DOI:10.1007/s11164-011-0344-5

Res Chem Intermed (2012) 38:251–259
DOI 10.1007/s11164-011-0344-5
Practical synthetic approach to 4-acetoxy-2-azetidinone
for the preparation of carbapenem and penem
antibiotics
•
Guo-Bin Zhou Yue-Qing Guan He Tang
•
•
•
Yan-Bin Zhao Li-Rong Yang
Received: 30 May 2011 / Accepted: 20 June 2011 / Published online: 7 July 2011
Ó Springer Science+Business Media B.V. 2011
Abstract A practical synthesis of 4-acetoxy-2-azetidinone useful for the prepa-
ration of carbapenem- and penem-type antibiotics is described. The synthesis has
advantages such as avoiding the tedious and costly column chromatographic or
recrystallized separation steps for diastereomers. The overall yield of the product is
greatly improved and the process is also more economical for large-scale produc-
tion. In addition, the mechanism for oxidative decarboxylation is also present.
Keywords Practical synthesis ꢀ 4-Acetoxy-2-azetidinone ꢀ Mechanism ꢀ
Oxidative decarboxylation
Introduction
(3R,4R)-4-Acetoxy-3-[(10R-tert-butyldimethylsilyloxy)ethyl]-2-azetidinone (4-AA)
(Fig. 1) and its derivatives are well known to be highly versatile intermediates for
the synthesis of thienamycin and carbapenem derivatives and other novel antibiotics
that might defeat bacterial resistance [1–4]. With possible industrial developments,
a tremendous amount of effort has been devoted to the search for efficient
preparations of this chiral azetidinone (4-AA) and a variety of methods for
G.-B. Zhou (&) ꢀ L.-R. Yang (&)
Department of Chemical and Biochemical Engineering, Zhejiang University,
Hangzhou 310027, China
e-mail: gbzhou_zju@126.com
L.-R. Yang
e-mail: lryang@zju.edu.cn
G.-B. Zhou ꢀ Y.-Q. Guan ꢀ H. Tang ꢀ Y.-B. Zhao
Zhejiang Hisoar Pharmaceutical Co., LTD., No.100 Waisha Branch Rd.,
Jiaojiang Taizhou, Zhejiang 318000, China
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G.-B. Zhou et al.
Fig. 1 Structure of (3R,4R)-
4-acetoxy-3-[(10R-tert-
butyldimethylsilyloxy)ethyl]-
2-azetidinone
Si
O
H
OAc
Me
NH
O
synthesizing this compound have been performed such as [2 ? 2] cycloadditions of
ketenes to Schiff bases, using optically active natural sources and so on [5–8].
Though some of these have been industrialized and have succeeded in mass
production of the compound, they involve various common problems in that the cost
of starting materials is very high, large quantities of solvents and reagents for
extensive column chromatographic separation of diastereomers are required, and the
overall yield is still low, in spite of using advanced industrial techniques.
Results and discussion
Our considerable current research interest in the industrial synthesis of (3R,4R)-
4-acetoxy-3-[(10R-tert-butyldimethylsilyloxy)ethyl]-2-azetidinone (4-AA) is sup-
ported by Lee’s work, etc. [9, 10] using L-threonine as the optically active source
(Scheme 1).
During our research, we found some industrial synthetic problems in the above
process: (1) In the C3–C4 b-lactam ring formation, a significant amount of
stereoisomer (2b) is produced, which needs to be separated by the tedious and costly
column chromatographic or recrystallized separation step. (2) The stereoisomer 2b
had to be discarded because of an unknown impurity, which was produced when 3b
was hydrolyzed. (3) The overall yield of the product is still low.
In order to overcome the industrial synthetic problems mentioned above, we
developed a practical, scalable, and economical procedure for synthesis of 4-AA.
Our synthetic strategy is shown in Scheme 2.
As shown in Scheme 2, ethyl 2-((2R,3R)-N-(4-methoxyphenyl)-3-methyloxirane-
2-carboxamido)acetate (1) was derived in high yield from L-threonine according to a
known method [11]. This epoxy amide (1) was then cyclized with 1 N lithium
hexamethyldisilazide (LiHMDS) in THF at -20 °C to give ethyl 3-((R)-1-hydroxy-
ethyl)-1-(4-methoxyphenyl)-4-oxoazetidine-2-carboxylate (2a and 2b) in 89% yield,
in which the diastereomeric ratio is about 6:1. Hydrolyzation of (2a and 2b) with 1 N
NaOH in ethanol to afford 3-((R)-1-hydroxyethyl)-1-(4-methoxyphenyl)-4-oxoaze-
tidine-2-carboxylic acid (3a0 and 3b0) in quantitative yield, which was protected with
tert-butyldimethylsilyl chloride in DMF at 35 °C for 10 h to give 3-((R)-1-(tert-
butyldimethylsilyloxy)ethyl)-1-(4-methoxyphenyl)-4-oxoazetidine-2-carboxylic
acid (4a and 4b) in 95% yield. Acetoxylation of (4a and 4b) was accomplished with
123

Practical synthetic approach to 4-acetoxy-2-azetidinone
253
OH
O
COOH
(1) NaNO2/HCl
CH2CO2C2H5
Me
LiN(SiMe3)2
TBDMSO
Me
C
N
NH2
(2) ClCOOC2H5, Et3N
PMP NHCH2CO2C2H5
O
PMP
(L)-threonine
1
TBDMSO
OH
H
OH
H
H
C
CO2C2H5
PMP
CO2C2H5
H
C
CO2C2H5
CO2C2H5
Me
Me
TBDMSCl
Me
Me
C
N
C
N
N
N
O
O
PMP
O
O
PMP
PMP
2a
2b
3b
3a
TBDMSO
Me
TBDMSO
Me
H
C
H
C
CO2H
+
CO2H
PMP
Pb (OAc)4
unknown impurity
90%
NaOH
N
N
O
PMP
O
4b 10%
4a
TBDMSO
H
TBDMSO
Me
H
C
OAc
OCOCH3
O3
Me
NH
O
N
O
PMP
4-AA
5a
PMP =
TBDMS=
OMe
Si
Scheme 1 Synthesis of (3R,4R)-4-acetoxy-3-[(10R-tert-butyldimethylsilyloxy)ethyl]-2-azetidin-one
(4-AA)
Pb3O4 in acetic acid to stereoselectively afford (2R,3R)-3-((R)-1-(tert-butyldi-
methylsilyloxy)ethyl)-1-(4-methoxyphenyl)-4-oxoazetidin-2-yl acetate (5a) in
96% yield [12]. At last, the product (5a) reacted with ozone in methanol at
-20 °C followed by reductive work-up to give 4-AA in 95% yield [13, 14]. It is
noteworthy that separation of stereoisomers (2a and 2b) is not needed, diastereo-
mers 2b, 3b0, and 4b all can be converted into target compound without being
discarded, and the overall yield of the product is greatly improved in this process.
Acetoxylation reaction is a key step for stereoselective synthesis of 4-AA. In our
study, the acetoxylation reaction of 4a, 4b, and the mixture of 4a and 4b were
examined with Pd3O4 in acetic acid at 50 °C. The results are shown in Table 1.
When 4a, 4b or the mixture of 4a and 4b was treated with Pd3O4 in acetic acid at
50 °C respectively, an unexpected process took place and all gave only one product
of trans-isomer 5a, without containing any of the cis-isomer 5b. Therefore, the
possible mechanism we deduced is shown in Scheme 3 [15–19].
123

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G.-B. Zhou et al.
OH
O
COOH
1. NaNO2/HCl
CH2CO2C2H5
Me
LiN(SiMe3)2
Me
C
N
NH2
2. ClCOOC2H5, Et3N
PMP NHCH2CO2C2H5
O
PMP
(L)-threonine
1
OH
H
OH
H
OH
H
OH
H
CO2H
CO2C2H5
+
CO2H
+
CO2C2H5
Me
Me
Me
Me
1. 1N NaOH
2. 1N HCl
C
N
C
N
C
N
C
N
O
O
N
O
O
PMP
PMP
PMP
PMP
2a
2b
3b'
3a'
TBDMSO
Me
TBDMSO
Me
H
C
H
C
CO2H
CO2H
PMP
Pb (OAc)4
TBDMSCl
+
N
O
O
PMP
4a
4b
TBDMSO
TBDMSO
H
H
OAc
OCOCH3
O3
Me
Me
NH
C
N
O
O
PMP
4-AA
5a
OMe
PMP =
TBDMS=
Si
Scheme 2 Practical
2-azetidinone (4-AA)
synthesis
of
(3R,4R)-4-acetoxy-3-[(10R-tert-butyldimethylsilyloxy)ethyl]-
Table 1 Results of acetoxylation reaction of 4a, 4b, and the mixture of 4a and 4b
Entry
Reactant
Product
Yieldsa (%)
1
2
3
a
4a
5a
5a
5a
97
4b
96.5
96
4a and 4b(4a:4b = 6:1)
Isolated yields
The reaction of 4a (or 4b) with the oxidizing agent was expected to go through
the lead(IV)carboxylate intermediate, which would decompose to an alkyl radical.
The acyliminium cation was formed after the free radical has undergone a one-
electron oxidation, which can smoothly react with nucleophiles because it was
stabilized by adjacent nitrogen. In order to confirm the formation of a four-
membered acyliminium ion, the oxidation of 4a in the mixture of AcOH and water
was carried out and we obtained the expected products 5a and (R)-3-(1-(tert-
butyldimethylsilyl-oxy)ethyl)-1-(4-methoxyphenyl)azetidine-2,4-dione (Fig. 2).
123

Practical synthetic approach to 4-acetoxy-2-azetidinone
255
TBDMSO
TBDMSO
Me
H
CO2H
PMP
H
C
H
C
CO2Pb(OAc)3
PMP
Me
Pb(OAc)4
Me
CO2
+
C
N
N
N
O
O
O
PMP
4a(or 4b)
TBDMSO
b
TBDMSO
Me
TBDMSO
OAc
a
H
C
H
C
H
C
OCOCH3
PMP
Me
Pb(IV)
Me
N
N
N
O
O
O
PMP
PMP
5a
Acyliminium cation
PMP =
OMe
TBDMS=
Si
Acyliminium cation
5a
Scheme 3 The possible mechanism of acetoxylation reaction
TBDMSO
Me
Fig. 2 Structure of (R)-
3-(1-(tert-butyldimethylsilyl-
oxy)ethyl)-1-(4-
methoxyphenyl)azetidine-
2,4-dione
H
C
O
N
O
PMP
According to the key transition state, the acyliminium cation is preferably
attacked by acetate anion from the less sterically hindered side (from the
side opposite the (tert-butyldimethylsilyloxy)ethyl) to produce 5a in high
stereoselectivity.
Conclusions
In conclusion, we have developed a practical, scalable, and economical procedure
for the synthesis of 4AA, which has advantages such as avoiding the tedious
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G.-B. Zhou et al.
and costly column chromatographic or recrystallized separation steps for diaste-
reomers, diastereomers (4a, 4b) all can be stereoselectively converted into product
(5a), the overall yield of the product (4-AA) is greatly improved, and the process is
more economical for large-scale production. Further work is currently going on to
extend our synthetic protocol.
Experimental section
General commercially available chemicals were all reagent-grade. Melting points
(mp) were determined on a Buchi 535 capillary melting apparatus. Optical rotations
were obtained using a JASCO DIP-1000 polarimeter at room temperature using the
sodium D line. The [1]H-NMR and [13]C-NMR spectra were recorded in CDCl3 or
DMSO-d6 on a Mercury Plus Varian 400-MHz FT-NMR spectrometer, using TMS
as the internal standard. ESI/MS were acquired on a Thermo Scientific LCQ
spectrometer. IR spectra were determined on a Nicolet NEXUS-470 FT-IR
spectrometer as KBr pellets. Analytical TLC was performed on a Merck precoated
TLC (silica gel 60 F254) plate.
Preparation of ethyl 2-((2R,3R)-N-(4-methoxyphenyl)-3-methyloxirane-
2-carboxamido)acetate 1
This compound was obtained as yellow oil according to the known procedures
20
[20–23]. Yield: 80%, ½aꢁD ¼ þ20:7ꢂ (c = 1.0, CHCl3). [1]H-NMR: 1.25 (t, J = 4.0,
3 H), 1.41 (d, J = 5.6, 3 H), 3.04 (m, 1 H), 3.29 (d, J = 4.8, 1 H), 3.82 (s, 3 H), 4.15
(m, 3 H), 4.62 (d, J = 16.8, 1 H), 6.93 (m, 2 H), 7.27 (m, 2 H). [13]C-NMR: 168.37,
166.84, 159.24, 133.12, 128.89, 114.74, 61.23, 55.42, 54.12, 53.59, 51.34, 14.13,
13.14. m/z (ESI): 316.3 [M ? Na]?. IR (KBr): m 3,485, 2,980, 2,937, 2,839, 1,747,
1,681, 1,606, 1,583, 1,512, 1,433, 1,396, 1,373, 1,300, 1,249, 1,199, 1,107, 1,026,
970, 839 cm-1
.
Preparation of ethyl 3-((R)-1-hydroxyethyl)-1-(4-methoxyphenyl)-
4-oxoazetidine-2-carboxylate 2a and 2b
To a solution of 1 (58.6 g, 0.2 mol) in THF under nitrogen, 1 N lithium
hexamethyldisilazide LiN(SiMe3)2 solution (240 mL) was added dropwise at
-40 °C. After 3 h of stirring, the solution was allowed to slowly warm to -20 °C.
The reaction was monitored by TLC. After this was accomplished, the reaction was
quenched with excess AcOH, and diluted with EtOAc, washed with sat. NaHCO3
and brine, dried over MgSO4, and concentrated in vacuo. The residue was
purified by recrystallization from toluene/n-hexane to give 52.0 g of 2a and 2b as
light yellow powder. Analytical samples were further purified by column
chromatography.
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Practical synthetic approach to 4-acetoxy-2-azetidinone
20
257
2a: m.p. 93.5–95.0°. ½aꢁD ¼ ꢃ115:2ꢂ (c = 1.0, CHCl3). [1]H-NMR: 1.19 (m, 6
H), 3.38 (t, J = 2.8, 1 H), 3.71(s, 3 H), 4.08 (m, 1 H), 4.18 (m, 2 H), 4.63 (d,
J = 2.8, 1 H), 5.20 (d, J = 4.8, 1 H), 6.93 (d, J = 8.8, 2 H), 7.21 (d, J = 8.8, 2 H).
[13]C-NMR: 169.94, 163.69, 155.36, 130.75, 117.25, 114.20, 62.57, 62.11, 61.17,
55.23, 52.00, 21.83, 14.04. m/z (ESI): 294.2 [M ? H]?. IR (KBr): m 3,425, 2,964,
2,956, 2,935, 2,908, 1,724, 1,587, 1,518, 1,447, 1,411, 1,375, 1,338, 1,300, 1,255,
1,209, 1,165, 1,132, 1,118, 1,030, 877, 833, 804 cm-1
.
20
2b: m.p. 164.0–165.5°. ½aꢁD ¼ þ71:0ꢂ (c = 1.0, CH3OH). [1]H-NMR: 1.21 (m, 6
H), 3.57 (m, 1 H), 3.70 (s, 3 H), 3.93 (m, 1 H), 4.15 (m, 2 H), 4.73 (d, J = 5.6, 1 H),
4.91 (d, J = 6.0 Hz, 1 H), 6.91 (d, J = 8.8, 2 H), 7.15 (d, J = 8.8, 2 H). [13]C-
NMR: 169.68, 163.47, 155.41, 130.65, 117.16, 114.28, 62.52, 60.99, 59.97, 55.22,
53.81, 22.65, 13.98. m/z (ESI): 294.1 [M ? H]?. IR (KBr): m 3,508, 2,974, 2,937,
1,739, 1,716, 1,581, 1,514, 1,444, 1,404, 1,363, 1,301, 1,251, 1,220, 1,168, 1,114,
1,091, 1,066, 1,030, 898, 833, 815 cm-1
.
Preparation of 3-((R)-1-hydroxyethyl)-1-(4-methoxyphenyl)-4-oxoazetidine-2-
carboxylic acid 3a0 and 3b0
To a stirred solution of 2a and 2b (45.8 g, 0.156 mol) in EtOH (100 mL) was added
gradually 1 N-NaOH (187 mL) at room temperature, then the solution was allowed
to warm to 50 °C. After stirring for 30 min, the reaction mixture was concentrated
in vacuo and diluted with H2O, washed with ethyl acetate. The aqueous phase was
acidified to pH = 2 with 1 N-HCl, filtered and washed with n-hexane to give 39.7 g
of 3a0 and 3b0 as a white solid which was employed for the next reaction. Analytical
samples were further purified by recrystallization.
20
3a0: m.p. 179.5–181.5°. ½aꢁD ¼ ꢃ105:8ꢂ (c = 1.0, DMF). [1]H-NMR: 1.18 (m, 3
H), 3.31 (q, J = 2.4, 1 H), 3.71 (s, 3 H), 4.05 (m, 1 H), 4.50 (m, 1 H), 5.14 (s, 1 H),
6.91 (m, 2 H), 7.15 (m, 2 H). [13]C-NMR: 171.54, 163.81, 155.25, 130.90, 117.16,
114.21, 62.65, 61.94, 55.25, 52.08, 21.83. m/z (ESI): 266.2 [M ? H]?. IR (KBr):
m 3,400, 2,974, 2,843, 2,729, 2,615, 2,536, 1,743, 1,712, 1,583, 1,514, 1,442, 1,375,
1,352, 1,300, 1,247, 1,178, 1,128, 1,082, 1,024, 968, 927, 871, 835, 812 cm-1
.
20
3b0: m.p. 194.5–196.5°. ½aꢁD ¼ þ85:5ꢂ (c = 1.0, DMF). [1]H-NMR: 1.24 (m, 3
H), 3.52 (q, J = 5.6, 1 H), 3.70 (s, 3 H), 3.97 (q, J = 6.0, 1 H), 4.60 (d, J = 6.0,
1 H), 6.91 (m, 2 H), 7.15 (m, 2 H). [13]C-NMR: 170.08, 163.56, 155.31, 130.83,
117.14, 114.27, 62.57, 59.76, 55.26, 54.09, 22.58. m/z (ESI): 266.1 [M ? H]?. IR
(KBr): m 3,412, 2,937, 2,630, 2,538, 1,739, 1,701, 1,581, 1,516, 1,458, 1,444, 1,400,
1,301, 1,246, 1,174, 1,136, 1,114, 1,084, 1,030, 891, 831 cm-1
.
Preparation of 3-((R)-1-(tert-butyldimethylsilyloxy)ethyl)-1-
(4-methoxyphenyl)-4-oxoazetidine-2-carboxylic acid 4a and 4b
A mixture of 3a0 and 3b0 (31.8 g, 0.12 mol), tert-butylmethylsilyl chloride (47.2 g,
0.288 mol), triethylamine (29.0 g 0.288 mol) in DMF (300 mL) was allowed to
123

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G.-B. Zhou et al.
stand at 35 °C for 10 h. The reaction mixture was diluted with ethyl acetate, washed
with 1 N HCl, sat. NaHCO3 and brine, dried over MgSO4 and concentrated in
vacuo. The residue was purified by recrystallization from MeOH/H2O to give 44.8 g
of 4a and 4b as a white solid. Analytical samples were further purified by column
chromatography.
20
4a: m.p. 189.0–191.0°. ½aꢁD ¼ ꢃ121:1ꢂ (c = 1.0, CHCl3). [1]H-NMR 0.00 (s, 3
H), 0.07 (s, 3 H), 0.74 (s, 9 H), 1.27 (d, J = 6.0 Hz, 3 H), 3.40 (s, 1 H), 3.77 (s, 3
H), 4.36 (q, J = 2.4, 1 H), 4.63 (d, J = 2.0, 1 H), 6.83 (d, J = 9.2, 2 H), 7.25 (d,
J = 9.2, 2 H), 11.53 (s, 1 H). [13]C-NMR: 175.13, 164.20, 156.17, 130.47, 117.87,
114.20, 64.16, 62.82, 55.43, 51.99, 25.58, 22.39, 17.78, -4.20, -5.02. m/z (ESI):
380.2 [M ? H]?. IR (KBr): m 2,964, 2,931, 2,858, 2,615, 1,751, 1,716, 1,589, 1,512,
1,444, 1,394, 1,361, 1,334, 1,294, 1,246, 1,211, 1,153, 1,139, 1,116, 1,070, 1,039,
976, 829 cm-1
.
20
4b: m.p. 119.1–120.5° Yellow crystals ½aꢁD ¼ þ32:6ꢂ (c = 1.0, CHCl3). [1]H
NMR: 0.04 (m, 6 H), 0.82 (s, 9 H), 1.38 (d, J = 6.4, 3 H), 3.60 (m, 1 H), 3.75 (s, 3 H),
4.47 (q, J = 5.6, 1 H), 4.59 (d, J = 5.6, 1 H), 6.79 (d, J = 9.2, 2 H), 7.21 (d, J = 9.2, 2
H). [13]C-NMR: 173.68, 163.73, 156.20, 130.52, 118.117, 114.21, 65.15, 61.40,
55.47, 54.14, 29.77, 25.79, 21.90, 18.06, -4.17, -4.74. m/z (ESI): 380.1 [M ? H]?.
IR (KBr): m 3,315, 2,953, 2,931, 2,854, 1,735, 1,708, 1,587, 1,512, 1,440, 1,398, 1,363,
1,301, 1,244, 1,193, 1,153, 1,105, 1,037, 989, 964, 920, 825 cm-1
.
Preparation of (2R,3R)-3-((R)-1-(tert-butyldimethylsilyloxy)ethyl)-
1-(4-methoxyphenyl-4-oxoazetidin-2-yl acetate 5a
Pb3O4 (67.5 g. 0.098 mol) was added to the mixture of glacial acetic acid (60 mL)
and acetic anhydride (60 mL) by portionwise at 50 °C. After 2 h, the suspension of
4a and 4b (30.0 g, 0.079 mol) in glacial acetic acid (60 mL) was added dropwise to
the above reaction mixture. The reaction was monitored by TLC, and after being
accomplished, the reaction was quenched by the addition of 1 mL of ethyleneglycol
and was concentrated in vacuo. The residue was solidified with a large excess of
20
H2O to give 29.8 g of 5a. m.p. 76.5–77.5°. ½aꢁD ¼ ꢃ72:9ꢂ (c = 1.0, CHCl3). [1]H-
NMR: 0.00 (s, 3 H), 0.06 (s, 3 H), 0.74 (s, 9 H), 1.31 (d, J = 6.4, 3 H), 2.12 (s, 3 H),
3.19(d, J = 2.4, 1 H), 3.77 (s, 3 H), 4.28 (m, 1 H), 6.61 (s, 1 H), 6.84 (m, 2 H), 7.30
(q, J = 2.0, 2 H). [13]C-NMR: 169.81, 163.54, 156.25, 129.47, 118.38, 114.20,
76.62, 65.35, 64.13, 55.41, 25.61, 22.34, 21.17, 17.79, -4.18, -5.05. m/z (ESI) 394
(M ? H)?. IR (KBr): m 2,949, 2,931, 2,858, 1,753, 1,512, 1,402, 1,375, 1,247,
1,226, 1,180, 1,151, 1,068, 1,028, 979, 898, 831 cm-1
.
Preparation of (3R,4R)-4-acetoxy-3-[(10R-tert-butyldimethylsilyloxy)
ethyl]-2-azetidinone 4-AA
A solution of 5a (19.6 g, 0.05 mol) in methanol (100 mL) was treated with ozone at
-20 °C until the starting material completely disappeared. Then, 10% aqueous
123

Practical synthetic approach to 4-acetoxy-2-azetidinone
259
sodium thiosulfate solution (337.5 mL) was added at 8 °C. After 1 h, thiourea
(11.4 g) was added portionwise. After stirring 3 h at 40 °C, the organic solvent was
removed partly in vacuo, and the residue was solidified with a large excess of H2O
and purified by recrystallization from with n-hexane to give 4-AA as white crystals.
20
m.p. 106–107°. Literature [23]. m.p. 104°. ½aꢁD ¼ þ51:5ꢂ (c = 1.0, CHCl3). [1]H-
NMR: 0.01 (d, J = 6.0, 6 H), 0.80 (s, 9 H), 1.19 (d, J = 6.4, 3 H), 2.04 (s, 3 H),
3.11(t, J = 2.4, 1 H), 4.14 (m, 1 H), 5.76 (s, 1 H), 7.04 (s, 1 H). [13]C-NMR: 170.7,
166.4, 74.9, 64.8, 63.7, 25.6, 20.8, 20.5, 17.8, -4.4, -5.1. m/z (ESI) 310
(M ? Na)?. IR (KBr): m 3,203, 2,958, 2,929, 2,895, 2,856, 1,782, 1,745, 1,471,
1,377, 1,361, 1,342, 1,300, 1,253, 1,234, 1,163, 1,134, 1,107, 1,078, 1,039, 983,
945, 896, 873 cm-1
.
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