Carbohydrate-based approach to four enantiomerically pure 2-naphthylmethyl 3-hydroxy-2-methylbutanoates

Article abstract of DOI:10.1016/j.tetlet.2007.12.104

Chiral pool approach using d-glucose, l-xylose, and d- and l-arabinoses was used to obtain four stereoisomeric 3-hydroxy-2-methylbutanoic acids with well defined configurations. The acids were isolated as fluorescent 2-naphthylmethyl esters after reaction with 2-naphthyldiazomethane.

Full text of DOI:10.1016/j.tetlet.2007.12.104

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1331–1335
Carbohydrate-based approach to four enantiomerically pure
2-naphthylmethyl 3-hydroxy-2-methylbutanoates
Bogdan Doboszewski , Piet Herdewijn *
Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, 300 Leuven, Belgium
Received 22 November 2007; revised 13 December 2007; accepted 18 December 2007
Available online 14 January 2008
Abstract
Chiral pool approach using D-glucose, L-xylose, and D- and L-arabinoses was used to obtain four stereoisomeric 3-hydroxy-2-methyl-
butanoic acids with well defined configurations. The acids were isolated as fluorescent 2-naphthylmethyl esters after reaction with
2-naphthyldiazomethane.
Ó 2008 Elsevier Ltd. All rights reserved.
The compound (2E,10Z,12E)-20-((3-aminocarboxy)-2-
methyl-1-oxybutyl)amino-7-methylene-17-oxo-19-oxy-3,5,
15-trimethyl-eicosa-2,10,12-trienoic acid has been isolated
from Pseudomonas batumici1 and found to be active against
Staphylococcus aureus. The compound has five stereogenic
centers from which the chirality has not been determined.
Here we describe the synthesis of four stereoisomeric
3-hydroxy-2-methylbutanoic acids, isolated in the form
of fluorescent 2-napthylmethyl esters, from carbohydrate
precursors. These reference compounds are used to solve
the chirality of two of the stereogenic centers of the target
compound. The target compounds 6, 14, 20, and 23 were
The basic idea of transformation of chirality present in
four starting sugar derivatives 1, 7, 16, and 21 into the chi-
rality in targets 6, 14, 20, and 23, respectively, is shown in
Figure 1. In all cases the configurations at the C4 atoms in
substrates 1, 7, 16, and 21 and in the intermediate 3,5-di-
deoxy-3-C-methylpentofuranoses 4, 13, 19, and 22, respec-
tively, were preserved, whereas orientation of the bulky
1,2-O-isopropylidene group present in 1, 7, 16, and 21
served as a steric bias to obtain predictably the necessary
orientation of the C3 methyl groups in 4, 13, 19, and 22
(see Schemes 1–3). Finally, the stereogenic centers at atoms
C3 and C4 in 4, 13, 19, and 22 became those at atoms C2
and C3 in targets 6, 14, 20, and 23, respectively.
1
obtained as pure enantiomers within accuracy of their H
500 MHz measurements.
The synthesis of 2-naphthylmethyl-(3R)-hydroxy-(2R)-
methyl-butanoate 6 is shown in Scheme 1. 1,2;5,6-Di-O-
isopropylidene-a-D-glucofuranose 1 was oxidized with a
CrO3–Py–Ac2O mixture by analogy to similar transforma-
tions,14,15 followed by the Wittig methylenation and hydro-
genation over Adams catalyst to furnish a mixture of the
allo:gluco epimers in ca. 10:1 proportion.16,17 Flash chro-
matography could be used to obtain the necessary more
polar allo epimer, but it was much more convenient to per-
form ‘dehomologation’ by analogy to the other derivatives
of D-glucofuranose,18,19 and subsequent tosylation to
obtain 3-deoxy-1,2-O-isopropylidene-3C-methyl-5-O-p-tolue-
nesulfonyl-a-D-ribofuranose 3 as a pure stereoisomer by
Optically active 3-hydroxy-2-methylbutanoic acids with
variable ee were obtained previously using different ver-
sions of the aldol condensation,2–10 eventually amended
by enzymic resolution,2,3 or by enantioselective reductions
of the carbonyl groups11,12 or acetoxymercuration followed
by resolution13 as the critical steps.
*
Corresponding author. Tel.: +32 16 337387; fax: +32 16 337340.
E-mail address: piet.herdewijn@rega.kuleuven.be (P. Herdewijn).
On leave from the Departamento de Quimica, UFRPE, 52171-900
Recife, Brazil.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.12.104

1332
B. Doboszewski, P. Herdewijn / Tetrahedron Letters 49 (2008) 1331–1335
O
H3C
H3C
CH3
O
CH3
O
O
R OH
R
OH
OH
H
H
CO2R
O
O
CH3
CH3
CH3
6
CH3
OH
O
O
D
-Glc
1
4
R =
CH2
Ph2
CH3
R
O
CH3
CH3
Si
O
O
CH3
t
Bu
OH
OH
HO
H
H3C
S
CH3
CO2R
H
HO
-Ara
D
7
13
14
H
O
O
O
S OH
S
CH3
CH3
OH
HO
H3C
H3C
CH3
O
t
Bu
CO2R
Si
O
H3C
(CH3)2
H
HO
L-Xyl 16
19
20
H
S
O
O
OH
OH
H3C
OH
Ph2
Si
H
CO2R
O
O
H3C
R
CH3
CH3
O
t
Bu
CH3
OH
CH3
L-Ara 21
22
23
Fig. 1. Synthetic strategy to obtain the four stereoisomeric 3-hydroxy-2-methylbutanoic acids.
O
O
H3C
H3C
1. LiHB(Et)3,THF,rt
2. 2M H2SO4
TsO
1. CrO3,Py,Ac2O
O
1. H5IO6,EtOAc
O
2. Ph3P CH3,BuLi, THF
73% for two steps
CH3
CH3
2. NaBH4,EtOH
94% two steps
3. TsCl,Py
1
O
Br
O
O
CH3
CH3
allo:gluco 10:1
O
50% for two steps
CH3
-ribo epimer
CH3
D
3. Pt2O, H2 95%
3
54% (cryst. from EtOAc)
2
CH3
CH3
O
1. NaIO4,EtOH,H2O
5
6
R =
OR
CHO
H
OH
O
NH4OH,MeOH
H
2. NaClO2,NaH2PO4
35% H2O2,CH3CN
H
COCH2
74% for four steps
CH3
OH
CH3
CHN2
3.
4
CH2Cl2
Scheme 1. Synthesis of the (3R)-hydroxy-(2R)-methyl butanoate.
crystallization from EtOAc. The configuration at the C3
atom was confirmed by X-ray analysis.20
with yellow HgO and cat. KOH in CH2Cl2, 2 h, by analogy
to the other arylhydrazones26,27) furnished a mixture of 6
and less polar formate 5. Both compounds could be sepa-
rated by flash chromatography, but it was more convenient
to perform basic hydrolysis of the formate (NH4OH–
MeOH) and to isolate (3R,2R) target 6. 1H 500 MHz spec-
trum of this compound showed no traces of epimerisation
at C2 by comparison with the spectrum of the 3R,2S com-
pound 14 (see below).
Treatment with LiBH(Et)3/THF smoothly effected sub-
stitution at the C5 position. Hydrolysis of the acetonide
21
function (2 M H2SO4–H2O, rt; FeCl3–6H2O–CH2Cl2 or
I2–MeOH22 were totally inefficient) gave diol 4, which
was cleaved with NaIO4 and the formed aldehyde function
was oxidized to the carboxyl function using NaClO2–
23
H2O2–NaH2PO4 mixture in CH3CN for 1–2 h at rt
(AgO, THF/H2O24 was inefficient). Final esterification
with freshly prepared solution of 2-naphthyldiazomethane
(obtained by oxidation of 2-naphthylmethylhydrazone25
(3R,2S) Diastereoisomer 14 was obtained as shown in
Scheme 2. The t-butyldiphenylsilyl-1,2-O-isopropylidene-
b-D-arabinofuranose 7 was obtained by analogy to its

B. Doboszewski, P. Herdewijn / Tetrahedron Letters 49 (2008) 1331–1335
1333
OR
O
O
CH3
CH3
RO
O
OR
O
O
CH3
CH3
1. CrO3,Py,Ac2O
O
CH3
Pd/C, H2,EtOH
O
O
O
2. Ph3P CH3,BuLi
46%
9
CH3
CH3
OR
Br
CH2
+
56% for two steps
8
HO
O
O
O
CH3
CH3
92%
1.Bu4NF, THF,
2. PtO2, H2, EtOH
7
Me
R =
SitBuPh2
10 36%
OH
HO
O
O
O
O
CH3
CH3
CH3
CH3
CH3
O
O
+
71%
11
CH3
13%
12
1. Tf2O, Py, CH2Cl2
2. LiHB(Et)3
3. 2M H2SO4
CH3
CH3
see Scheme 1
(4 6)
O
OH
OH
O
HO
H
CH3
H3C
COCH2
13
27% for three steps
H
14
65% for four steps
Scheme 2. Synthesis of the (3R)-hydroxy-2(S)-methylbutanoate.
O
O
O
O
CH3
CH3
CH3
1. CrO3,Py,Ac2O
O
CH3
CH3
O
CH3
TsCl,Py
O
O
CH3
O
2. Ph3P CH3,BuLi
R
O
HO
TsO
Br
HO
CH3
18
70% for two steps
17
/xylo ca 10:1
3. Bu4NF 100%
pure
L
-ribo epimer, 69%
by cryst. from EtOAc
L
-xylose
4. PtO2, H2, EtOH
ribo
quantitative yield
R = H
Si
15
75%
BuMe2
t
75%
16
see Scheme 1 (3
CH3
4)
H
O
HO
O
OH
CH3
H3C
HO
see Scheme 1 (4 6)
H3C
COCH2
H
19 64% for two steps
20
51% for four steps
Scheme 3. Synthesis of the (3S)-hydroxy-(2S)-methylbutanoate.
L-enantiomer28,14,15 and converted to the 3-methylene
derivative 8 via oxidation, followed by Wittig reaction
(PH3–PCH3Br, BuLi, THF; Tebbe reagent or Peterson
olefination could also be used by analogy to the L-enantio-
mer14). Hydrogenation over Pd/C furnished a 46:36 mix-
ture of the less polar compound 9 with a migrated C@C
bond and the desired 3-C-deoxy-3-C-lyxo product 10.
Formation of 9 undoubtedly reflected an increased steric
congestion in the upper part of the furanosyl ring resulting
from the syn orientation of the four substituents in 10.
Also, it is known that tetrasubstituted olefins can be quite
resistant toward addition of hydrogen,29 so persistence of 9
under hydrogenation conditions is not unusual. In an
attempt to suppress the unwanted migration of the double
bond, a steric bulk in the upper part of the furanosyl ring
was decreased by desilylation and also the Adams catalyst
was used. Platinum is known to favor additions of H2 to
C@C bonds rather to catalyze their migrations.30 Thus,
application of the Adams catalyst permitted to obtain 11
in 71% yield accompanied by the less polar 12 formed in
13% yield. A tosylate derived from 11 was very unreactive
toward a substitution by strong nucleophilic (‘supernucleo-
philic’) hydride anion coming from LIBH(Et)3, in sharp
contrast with a behavior at 3, but of a corresponding tri-
flate reacted with this reagent even though decomposition
was evident by TLC. Hydrolysis of the acetonide function
furnished the 3,5-dideoxy-3C-methyl-D-lyxofuranose 13,
which was converted to 2-naphthylmethyl-(3R)-hydroxy-
(2S)-methylbutanoate 14 by analogy to the procedure
described above for 6.
A synthesis of the 2-naphthylmethyl (3S)-hydroxy-(2S)-
methylbutanoate 20, which is an enantiomer of 6, was

1334
B. Doboszewski, P. Herdewijn / Tetrahedron Letters 49 (2008) 1331–1335
based on relatively cheap L-xylose, rather than on L-glu-
cose. 1,2-O-Isopropylidene-a-L-xylofuranose was obtained
in a two-step one pot process by analogy to the D-enantio-
mer,31 and converted to its 5-O-t-butyldimethylsilyl ether
16 as described for D-form.18,32 Oxidation at the C3 posi-
tion followed by Wittig methylenation, desilylation, and
hydrogenation furnished a chromatographically insepara-
ble mixture of the 3-deoxy-1,2-O-isopropylidene-3C-
methyl-a-L-ribofuranose and the corresponding L-xylo
epimer in approximate proportion 10:1 in favor of the
necessary L-ribo product. Tosylation and crystallization
from EtOAc furnished pure L-ribo compound 18, which
was converted to 3,5-dideoxy-3C-methyl-L-ribofuranose
19, and further to 20 by the same procedure as described
for 4.
References and notes
1. Smirnov, V. V.; Churkina, L. N.; Perepnikhatka, V. I.; Mukvich, N.
S.; Garagulya, A. D.; Kiprianova, E. A.; Kravets, A. N.; Dovzhenko,
S. A. Appl. Biochem. Microbiol. 2000, 36, 46.
2. Neri, C.; Williams, J. M. J. Adv. Synth. Catal. 2003, 345, 835.
3. Neri, C.; Williams, J. M. J. Tetrahedron Lett. 2002, 43, 4257.
4. Roush, W. R.; Bannister, T. D.; Wendt, M. D.; Jablonowski, J. A.;
Scheidt, K. A. J. Org. Chem. 2002, 67, 4275.
´
´
5. Vicario, J. L.; Badıa, D.; Dominguez, E.; Rodrıguez, M.; Carrillo, L.
J. Org. Chem. 2000, 65, 3754.
6. Harris, R. C.; Cutter, A. L.; Weissman, K. J.; Hanefeld, U.; Timoney,
M. C.; Staunton, J. J. Chem. Res. 1998, 283.
7. Lutzen, A.; Ko¨ll, P. Tetrahedron: Asymmetry 1997, 8, 1193.
¨
8. Raimundo, B. C.; Heathcock, C. H. Synlett 1995, 1213.
9. Hoffmann, R. W.; Dresely, S. Chem. Ber. 1989, 122, 903.
10. Davis, S. G.; Dordor-Hedgecock, J. M.; Warner, P. Tetrahedron Lett.
1985, 26, 2125.
The last compound, 2-naphthylmethyl-(3S)-hydroxy-
(2R)-methylbutanoate 23 was obtained from L-arabino-
furanose 21 by analogy to its D-enantiomer.
11. Tai, A.; Morimoto, N.; Yoshikawa, M.; Uehara, K.; Sugimura, T.;
Kikukawa, T. Agric. Biol. Chem. 1990, 54, 1753.
12. Tai, A.; Imaida, M. Bull. Chem. Soc. Jpn. 1978, 51, 1114.
13. Maskens, K.; Polgar, N. J. Chem. Soc., Perkin Trans. 1 1973, 109.
14. Doboszewski, B.; Herdewijn, P. Tetrahedron 1996, 52, 1651.
15. Dahlman, O.; Garegg, P. J.; Mayer, H.; Schramek, S. Acta Chem.
Scand. B 1986, 40, 15.
16. Dang, H.-S.; Roberts, B. P. J. Chem. Soc., Perkin Trans. 1 2002, 1161.
17. Martin, O. R.; Nabinger, R. C.; Ali, Y.; Vyas, D. M.; Szarek, W. A.
Carbohydr. Res. 1983, 121, 302.
18. Robins, M. J.; Doboszewski, B.; Timoshchuk, V. A.; Peterson, M. A.
J. Org. Chem. 2000, 65, 2939.
19. Xie, M.; Berges, D. A.; Robins, M. J. J. Org. Chem. 1996, 61, 5178.
20. de Armas, H. N.; Doboszewski, B.; Herdewijn, P.; Blaton, N. Acta
Crystallogr. Sect. E 2007, 63, 2678.
21. Sen, S. E.; Roach, S. L.; Boggs, J. K.; Ewing, G. J.; Magrath, J. J.
Org. Chem. 1997, 62, 6684.
22. Szarek, W. A.; Zamojski, A.; Tiwari, K. N.; Ison, E. R. Tetrahedron
Lett. 1986, 27, 3827.
23. Dalcanale, E.; Montanari, F. J. Org. Chem. 1986, 51, 567.
24. Corey, E. J.; Gilman, N. W.; Ganem, B. E. J. Am. Chem. Soc. 1968,
90, 5616.
25. Asis, S. E.; Bruno, A. M.; Martinez, A. R.; Sevilla, M. W.; Gaozza, C.
H.; Romano, A. M.; Coussio, J. D.; Ciccia, G. Il Farmaco 1999, 54,
517–523.
It is interesting to note that attempts to invert the con-
figuration at the C3 position of 14 (i.e. to get 20 from 14)
via a Mitsunobu process (nBu3P, iPrO2C–N@N–CO2iPr,
2,4-dinitrobenzoic acid, THF) were futile. Secondly, the
esterifications with 2-naphthyldiazomethane were instanta-
neous, and were visually followed by a loss of red-orange
color of the reagent and evolution of nitrogen. In situ gen-
erated aryldiazomethanes are in general less than 85%
pure33 and by coincidence the impurities present in 2-naph-
thyldiazomethane used throughout this work interfered
with the isolation of the transiently formed formates, for
example, 5. For this reason, only in the case of glucose such
intermediate was isolated. Additional advantage of using 2-
naphthylmethyl esters besides their fluorescence is that they
are easily detectable on TLC since they form characteristic
brownish-red spots upon spraying with 2% solution of
CrO3 in 10% aq H2SO4 and heating. In contrast, underiv-
atized 3-hydroxy-2-methylbutanoic acids form faint yellow
spots on blue background using acid–base indicator bro-
mocresol green, albeit the sensitivity of this method is
rather low.34,35
26. Miller, J. B. J. Org. Chem. 1959, 25, 560.
27. Gutsche, C. D.; Jason, E. F. J. Am. Chem. Soc. 1956, 78, 1184.
28. Martin, O. R.; Rao, S. P.; El-Shenawy, H. A.; Kurz, K. G.; Cutler, A.
B. J. Org. Chem. 1988, 53, 3287.
29. Smith, M. B.; March, J. In March’s Advanced Organic Chemistry, 6th
ed.; Wiley-Interscience: New Jersey, 2007; p 1053.
30. Keith, J. In Comprehensive Organic Functional Group Transforma-
tions; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.; Pergamon,
1995; p 71.
The compounds presented here were characterized by
300 MHz or 500 MHz NMR and by high resolution mass
measurement.36
In summary, all four stereoisomeric 3-hydroxy-2-methyl-
butanoic acids were obtained starting from easily accessible
derivatives of D-glucose, L-xylose, and D- and L-arabinose.
The target acids were isolated as fluorescent37 2-naphthyl-
methyl esters.
´
´
ˇ
31. Moravcova, J.; Capkova, J.; Stanek, J. Carbohydr. Res. 1994, 263, 61.
32. Yoshimura, Y.; Sano, T.; Matsuda, A.; Ueda, T. Chem. Pharm. Bull.
1988, 36, 162.
33. Smets, G.; Boutemburg, A. J. Polym. Sci. A1 1970, 8, 3251.
34. Touchstone, J. C.; Dobbins, M. F. In Practice of Thin Layer
Chromatography, 2nd ed.; Wiley Interscience: New York, 1983; p 163.
35. Krebs, K. G.; Heusser, D.; Wimmer, H. In Thin-Layer Chromatogr-
apy. A Laboratory Handbook; Stahl, E., Ed.; Springer Verlag: Berlin,
1969; p 854.
36. Selected data of intermediates 4 and 13, and targets 6 and 14 derived
from them: 4: [a]D +13.2 (initial); +27.9 (after 30 min), c 5.7, CHCl3;
1H (500 MHz, CDCl3): 5.38 (d, J12 = 3.8 Hz) and 5.19 (s) H1; 5.11 (br
s, exchangeable, OH); 4.04 (t, J23 = J21 = 4.5 Hz) and 3.94 (d,
J23 = 4.3 Hz) H2; 3.89 (dq, JH–Me = 6.0 Hz, J43 = 10.2 Hz) and 3.86
(dq, JH–Me = 6.1 Hz, J43 = 10.3 Hz) H4; 3.70 and 3.28 (two br s,
Acknowledgments
We appreciate Mr. Bert Demarsin of the Department of
Chemistry for EI HRMS measurements, and Mrs. Stepha-
nie Vandenwaeyenbergh and Professor Jef Rozenski for
the electrospray HRMS. Dr. Natalya Dubyankova and
Mr. Luc Baudemprez of this Institute are acknowledged
1
for H 500 MHz spectra.

B. Doboszewski, P. Herdewijn / Tetrahedron Letters 49 (2008) 1331–1335
1335
exchangeable, OH); 2.01 (m of 14 lines, JHÀMe = 6.9 Hz, J34 ca.
9.6 Hz, J32 = 4.3 Hz) and 1.71 (m of 14 lines, JH–Me = 6.6 Hz,
J34 = 9.6 Hz, J32 ca. 5.5 Hz) H3; 1.28 (d, JMe–H = 6.2 Hz) and 1.18
(d, JMe–H = 6.1 Hz) terminal Me; 1.00 (d, JMe–H = 7.0 Hz) and 0.99
(d, JMeÀH = 6.9 Hz) terminal C2 Me.
6: [a]D À24.1, c 5, CHCl3; 1H (500 MHz, CDCl3): 7.85–7.82 (m, 4H)
and 7.51–7.44 (m, 3H) H aromatic; 5.32 (s, 2H, –OCH2–); 3.92 (m of
five broadened lines, J = 6.3 Hz, 1H, H3); 2.64 (br s, exchangeable, –
OH); 2.54 (m of five lines, J = 7.2 Hz, H2); 1.22 (d, J = 6.4 Hz, 3H,
terminal Me); 1.21 (d, J = 7.2 Hz, 3H, C2–Me).
13C (75 MHz, CDCl3): 175.66, 133.14, 133.09, 128.42, 127.95, 127.68,
127.29, 126.32, 126.29, 125.69, 69.44, 66.49, 47.06, 20.71, 14.05.
HRMS (electrospray): calculated for C16H18O3+Na+ = 281.11483,
found 281.11465.
13C (75 MHz, CDCl3): 102.29, 97.13, 80.91, 78.81, 75.51, 73.58, 44.84,
42.28, 20.68, 18.82, 9.73, 9.16.
Exact mass (EI, 50 eV) calculated for C6J12O3–OH = 115.07589,
found 155.07717.
13: [a]D +44.8 (initial); +32.3 (after 25 min), c 1.6, CHCl3; 1H
(500 MHz, CDCl3): 5.28 (d, J12 = 4.6 Hz) and 5.27 (d, J12 = 1.6 Hz)
H1; 4.42 (m of five lines, J4-Me = J34 = 6.6 Hz) and 4.12 (m of five
lines, J4-Me = J43 = 6.5 Hz) H4; 4.10 (dd, J21 = 5.1 Hz, J23 = 6.4 Hz)
and 4.08 (dd, J21 = 1.5 Hz, J23 = 5.4 Hz) H2; 2.46 (multiplet of 10
lines, J32 = 5.5 Hz, J34 = 7.3 Hz, J3-Me = 7.3 Hz) and 2.28 (m of six
lines, J = 7.0 Hz) H3; 1.22 (d, JMeÀH = 6.6 Hz) and 1.17 (d, JMe–
H = 6.6 Hz) terminal Me; 1.02 (d, JMeÀH = 7.3 Hz) and 0.98 (d,
JMeÀH = 7.3 Hz) C2–Me.
14: [a]D ꢀ+0.5, c 6, CHCl3; 1H (500 MHz, CDCl3 after D2O
exchange): 7.84–7.81 (m, 4H) and 7.50–7.43 (m, 3H) H aromatic, 5.30
(s, 2H, –OCH2–), 4.09 (dq, J32 = 4.0 Hz, J3-Me = 6.3 Hz, 1H, H3),
2.62 (br s, residual OH), 2.57 (dq, J23 = 3.9 Hz, J2-Me = 7.2 Hz, 1H,
H2), 1.22 (d, JMe-2 = 7.3 Hz, 3H, C2–Me), 1.17 (d, JMe-3 = 6.4 Hz,
3H, terminal Me).
13C (125 MHz, CDCl3): 175.70, 133.10, 133.07, 128.43, 127.93,
127.67, 127.35, 126.32, 126.30, 125.70, 67.95, 66.50, 45.57, 19.80,
10.98.
13C (75 MHz, CDCl3): 101.57, 96.46, 79.06, 77.14, 76.52, 73.52, 73.48,
38.99, 38.24, 17.86, 17.59, 8.23, 7.53.
HRMS (electrospray) calculated for C16H18O3+Na+ = 281.11483,
found 281.11477.
HRMS (EI, 50 eV) calculated for C6H12O3–CH3 = 117.05516, found
117.05431.
37. Matthees, D. P.; Purdy, W. C. Anal. Chim. Acta 1979, 109, 61.