266
L. J. Gooßen, A. Döhring
LETTER
Synthesis of Adipic Acid Benzyl Ethyl Ester (6s): A dried flask
was charged with adipic acid monoethyl ester (1s, 352 mg, 2.0
mmol), di-t-butyl dicarbonate (2a, 585 mg, 2.6 mmol), benzyl alco-
hol (5a, 210 ml, 2.0 mol), and DMAP (12.0 mg, 0.10 mmol). Dry ni-
tromethane (4 mL) was added by syringe and the reaction was
stirred overnight at 50 °C. After the reaction was complete (TLC),
EtOAc was added and the organic layer was washed consecutively
with 2 M HCl, NaHCO3 solution, H2O and brine. After drying with
MgSO4 and removal of the volatiles in vacuo, the product was ob-
tained in high purity. For spectroscopic characterization, the prod-
uct was filtered through a small plug of silica using hexane/CH2Cl2
(3:7) as eluent. After concentrating to dryness, 6s (509 mg, 96%)
References
(1) (a) Otera, J. Esterification. Methods, Reactions and
Applications; Wiley-VCH: Weinheim, 2003. (b) Greene, T.
W.; Wuts, P. G. M. Protective Groups in Organic Synthesis,
3rd Ed.; Wiley: New York, 1999, 369. (c) Patai, S. The
Chemistry Acid Derivatives, Vol. 1; Wiley: New York,
1979, 267. (d) Falbe, J. Methods in Organic Chemisry
(Houben-Weyl), 4th Ed.; Thieme: Stuttgart – New York,
1985, Vol. E5. (e) Haslam, E. Tetrahedron 1980, 36, 2409.
(2) For particularly effective systems, see for example:
(a) Ishihara, K.; Ohara, S.; Yamamoto, H. Science 2000,
290, 1140. (b) Wakasugi, K.; Misaki, T.; Yamada, K.;
Tanabe, Y. Tetrahedron Lett. 2000, 41, 5249. (c) Xiang, J.;
Toyoshima, S.; Orita, A.; Otera, J. Angew. Chem. Int. Ed.
2001, 40, 3670; Angew. Chem. 2001, 113, 3782. (d) Xiang,
J.; Orita, A.; Otera, J. Adv. Synth. Catal. 2002, 344, 84.
(3) (a) Chakraborti, A. K.; Basak, A.; Grover, V. J. Org. Chem.
1999, 64, 8014. (b) Merz, A. Angew. Chem., Int. Ed. Engl.
1973, 12, 846; Angew. Chem. 1973, 85, 868.
1
was obtained as a colorless oil. H NMR (300.1 MHz, CDCl3):
d = 7.41–7.26 (m, 5 H), 5.11 (s, 2 H), 4.11 (q, 3J = 7 Hz, 2 H), 2.42–
2.27 (m, 4 H), 1.74–1.60 (m, 4 H), 1.24 (t, 3J = 7 Hz, 3 H) ppm. 13
C
NMR (75.5 MHz, CDCl3): d = 173.3, 173.1, 136.0, 128.5, 128.1,
128.1, 66.1, 60.2, 33.9, 24.3, 14.2 ppm. MS (EI): m/z (%) = 264 (4),
[M]+, 236 (17), 157 (38), 130 (20), 111 (37), 91 (100), 55 (15).
HRMS (EI): m/z calcd for C15H20O4 [M]+: 264.136160; found:
264.136221.
(4) For examples, see (a) Johnstone, R. A. W.; Rose, M. E.
Tetrahedron 1979, 35, 2169. (b) Chevallet, P.; Garrouste,
P.; Malawska, B.; Martinez, J. Tetrahedron Lett. 1993, 34,
7409. (c) Wang, T.; Lui, A. S.; Cloudsdale, I. S. Org. Lett.
1999, 1, 1835.
The reactions in Table 2 and Table 3 were performed following the
above procedure. All products were isolated and characterized by
means of 1H NMR and 13C NMR as well as by GC-MS and HRMS.
(5) Shieh, W.-C.; Dell, S.; Repič, O. J. Org. Chem. 2002, 67,
Acknowledgment
2188.
(6) Staab, H. A. Angew. Chem. 1962, 74, 407.
(7) (a) Neises, B.; Steglich, W. Angew. Chem., Int. Ed. Engl.
1978, 17, 522; Angew. Chem. 1978, 90, 556. (b) Hassner,
A.; Alexanian, V. Tetrahedron Lett. 1978, 4475.
(8) Mitsunobu, O. Synthesis 1981, 1.
We thank Prof. Dr. M. T. Reetz for generous support and constant
encouragement, and the DFG, the FCI, and the BMBF for financial
support.
(9) (a) Takeda, K.; Akiyama, A.; Nakamura, H.; Takizawa, S.;
Mizuno, Y.; Takayanagi, H.; Harigaya, Y. Synthesis 1994,
1063. (b) Pozdnev, V. F. Int. J. Pept. Protein Res. 1992, 40,
407.
(10) Gooßen, L. J.; Döhring, A. Adv. Synth. Catal. 2003, 345,
943.
Synlett 2004, No. 2, 263–266 © Thieme Stuttgart · New York