Organic Process Research & Development
Article
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V.; Narisano, E.; Thea, S. Tetrahedron 1993, 49, 9501. (g) Guanti, G.;
Banfi, L.; Riva, R.; Zannetti, M. T. Tetrahedron Lett. 1993, 34, 5483.
(h) Guanti, G.; Banfi, L.; Riva, R.; Zannetti, M. T. Tetrahedron Lett.
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Lett. 1996, 37, 521. (j) Guanti, G.; Moro, A.; Narisano, E. Tetrahedron
Lett. 2000, 41, 3203. (k) Egri, G.; Fogassy, E.; Novak, L.; Poppe, L.
Tetrahedron: Asymmetry 1997, 8, 547. (l) Miyata, S.; Kumamoto, T.;
Ishikawa, T. Helv. Chim. Acta 2007, 90, 1420.
(2) (a) Asano, T.; Yamazaki, H.; Kasahara, C.; Kubota, H.; Kontani,
T.; Harayama, Y.; Ohno, K.; Mizuhara, H.; Yokomoto, M.; Misumi, K.;
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R.; Stafford, J. A.; Scorah, N., Salsbury, J. S.; Das, S. WO/2009/
129401, 2009.
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Tetrahedron: Asymmetry 1999, 19, 4455. (b) Yokomatsu, T.; Minowa,
T.; Murano, T.; Shibuya, S. Tetrahedron 1998, 54, 9341.
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E.; Williams, O. L. Org. Process Res. Dev. 2009, 13, 152. (b) Wiss, J.;
Fleury, C.; Heuberger, C.; Onken, U. Org. Process Res. Dev. 2007, 11,
1096.
Ethyl 2,2-dimethyl-1,3-dioxane-5-carboxylate (37).
To a solution of 36 (30 g, 115.3 mmol) in DMSO (50 mL),
LiCl (9.8 g, 231 mmol) and water (2.1 g, 117 mmol) were
added. The batch was heated to 160 °C and aged for 2 h, then
cooled to 0 °C. To the batch were added water (150 mL) and
EtOAc (300 mL), and the batch was then filtered. To the
resulting filtrate was added EtOAc (50 mL), and the organic
layer was washed with brine (50 mL) and concentrated in vacuo
to afford the desired crude 37 compound (10.1 g, 46.0% yield),
which was used in the next step without purification.
MS (GC, pos.) m/z: 189.0.
1H NMR (400 MHz, CDCl3): δ 4.22−4.28 (2H, m), 4.14−
4.20 (2H, m), 4.01−4.08 (2H, m), 2.27−2.80 (1H, m), 1.44
(3H, s), 1.41 (3H, s), 1.24−1.30 (3H, m).
Ethyl 3-Hydroxy-2-(hydroxymethyl)propanoate (38).
To a solution of 37 (8.0 g, 42.5 mmol) in MeOH (58 mL) was
added 6 M HCl (4 mL, 24 mmol) at 25 °C. The batch was aged
for 12 h at 25 °C, and then to the batch was added NaHCO3
(23 g, 274 mmol). The batch was then filtered and washed with
EtOAc (50 mL) twice. The filtrate was concentrated in vacuo to
afford the desired crude 38 (6.19 g, 98.1% yield), which was
used in the next step without purification.
MS (GC, pos.) m/z: 148.9.
1H NMR (400 MHz, CDCl3): δ 4.22 (2H, dd, J = 14.0, 7.2
Hz), 3.93−3.99 (4H, m), 2.73−2.78 (2H, m), 2.69−2.72 (1H,
m), 1.30 (3H, t, J = 7.2 Hz).
Ethyl (R,S)-3-{[tert-Butyl(diphenyl)silyl]oxy}-2-
(hydroxymethyl)propanoate (29). To a solution of 38
(0.76 g, 5.13 mmol) in acetonitrile (15 mL) was added
triethylamine (0.52 g, 5.14 mmol), and the mixture was cooled
to −10 °C. To the batch was added tert-butylchlorodiphenylsi-
lane (1.37 g, 4.98 mmol), and the batch was aged for 12 h at 25
°C. After concentration in vacuo, diisopropylether (40 mL) and
water (30 mL) were added to the batch, and the resulting
organic layer was washed with brine (10 mL) and concentrated
in vacuo. The residue was purified by SiO2 column
chromatography (n-heptane/EtOAc = 8/1 then 2/1) to afford
the desired 29, 1.19 g (60.0% yield).
(6) The cost of chiral auxiliary reagent is 58,000 yen/5 g (TCI) or
86,600 yen/5 g (Sigma-Aldrich).
(7) (a) Bates, H. A.; Farina, J.; Tong, M. J. Org. Chem. 1986, 51,
2637. (b) Colombo, M. I.; Zinczuk, J.; Bohn, M. L.; Ruveda, E. A.
Tetrahedron: Asymmetry 2003, 14, 717.
(8) We also attempted to crystallize compound 33 not only with
diisopropyl ether but also with other ethers, CPME, 2-Me THF, and
MTBE. However, the use of CPME, 2-Me THF, and MTBE has
higher solubility than diisopropyl ether, making it difficult to prevent
large loss to the filtrate or to crystallization in spite of combination
with n-heptane.
(9) (a) Herz, W.; Tocker, S. J. Am. Chem. Soc. 1955, 77, 3554.
(b) Fisher, L. E.; Caroon, J. M.; Jahangir; Stabler, S. R.; Lundberg, S.;
MS (FAB, pos.) m/z: 387.1, MS (FAB, neg.) m/z: 385.2.
1H NMR (400 MHz, CDCl3): δ 7.52−7.70 (4H, m), 7.37−
7.50 (6H, m), 4.10−4.20 (2H, m), 3.80−4.05 (4H, m), 2.77−
2.83 (1H, m), 2.29−2.34 (1H, m), 1.23−1.30 (3H, m), 1,04
(9H, s).
́
Muchowski, J. M. J. Org. Chem. 1993, 58, 3643. (c) Cortes, E. C.;
Romero, E. C.; Ramírez, F. G. J. Heterocycl. Chem. 1994, 31, 1425.
(11) Lipase AK Amano is from Pseudomonas fluorescens which is a
useful enzyme for enantioselective hydrolysis reactions. (a) Gais, H. J.;
Hemmerle, H.; Kossek, S. Synthesis 1992, 169. (b) Suemune, H.;
Takahashi, M.; Maeda, S.; Xie, Z.-F.; Sakai, K. Tetrahedron: Asymmetry
1990, 1, 425. (c) Yamazaki, T.; Ohnogi, T.; Kitazume, T. Tetrahedron:
Asymmetry 1990, 1, 215. (d) Aribi-Zouioueche, L.; Fiaud, J.-C.
Tetrahedron Lett. 2000, 41, 4085. (e) Daniele, B.; Lesma, G.;
Macecchini, S.; Passarella, P.; Silvani, A. Tetrahedron: Asymmetry
1999, 10, 4057. (f) Xie, Z.-F.; Suemune, H.; Sakai, K. Tetrahedron:
Asymmetry 1990, 1, 395.
AUTHOR INFORMATION
Corresponding Author
5478. Fax: +81-293-24-2708.
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Notes
The authors declare no competing financial interest.
(12) (a) Boyle, T. P.; Bremner, J. B.; Coates, J. A.; Keller, P. A.; Pyne,
S. G. Tetrahedron 2005, 61, 7271. (b) Isozaki, K.; Miki, K. Chem.
Commun. 2010, 46, 2947. (c) Arcadi, A.; Bernocchi, E.; Cacchi, S.;
Caglioti, L.; Marinelli, F. Tetrahedron Lett. 1990, 31, 2463.
(d) Papageorgiou, C. D.; Cubillo de Dios, M. A.; Ley, S. V.; Gaunt,
M. J. Angew. Chem., Int. Ed. 2004, 43, 4641.
ACKNOWLEDGMENTS
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We are grateful to Mr. S. Ieda for helpful discussions about the
new synthetic approach, and to Mr. H. Yamazaki and Dr. C.
Kasahara for their helpful discussions about the Medicinal
Chemistry synthetic route. We also thank Mr. K. Itoh for
analytical study.
REFERENCES
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(1) (a) Guanti, G.; Banfi, L.; Narisano, E. J. Org. Chem. 1992, 57,
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K
dx.doi.org/10.1021/op3001383 | Org. Process Res. Dev. XXXX, XXX, XXX−XXX