8858
S.T. Heller, R. Sarpong / Tetrahedron 67 (2011) 8851e8859
65 mmol) was added dropwise and the resulting mixture was stirred
and allowed to warm to room temperature over 16 h. The reaction
mixture was concentrated to a slurry and 200 mL hexanes was
added. The heterogeneous mixture was filtered through Celite, the
filtrate was dried with Na2SO4, filtered, and concentrated in vacuo to
tR 8.29 min (major), 9.05 min (minor), 99% ee. This chromato-
graphic method was used to determine the enantiomeric excess of
naproxen methyl ester produced using MImC as well as that from
the treatment of enantiopure ester with imidazole.
afford a pale yellow oil (8.21 g, 90%). 1H NMR (400 MHz, CDCl3)
d
7.33
4.5.11. N-Methoxy-N-methylindole-3-acetamide (41). Prepared us-
ing the general amidation procedure with 3-indoleacetic acid
(0.088 g, 0.5 mmol) to obtain a white solid (0.104 g, 96%). 1H NMR
(d, J¼1.8 Hz, 1H), 6.84 (d, J¼1.8 Hz, 1H), 3.97 (s, 3H), 2.63 (s, 3H).
Spectra were consistent with those reported previously.30
(400 MHz, CDCl3)
d
8.24 (s, 1H), 7.65 (dd, J¼7.7, 1.0 Hz, 1H), 7.34 (dd,
4.5.4. Methyl 2-ethyl-1-imidazolecarboxylate (14c). Prepared by
analogy to methyl 2-methyl-1-imidazolecarboxylate using
2-ethylimidazole to yield a pale yellow oil (3.50 g, 91%). 1H NMR
J¼8.1, 1.0 Hz, 1H), 7.22e7.08 (m, 3H), 3.92 (s, 2H), 3.67 (s, 3H), 3.22
(s, 3H). Spectra were consistent with those reported previously36
(500 MHz, CDCl3)
d
7.33 (s, 1H), 6.86 (s, 1H), 3.96 (s, 3H), 3.02 (q,
4.5.12. Z-Gly-N(Me)OMe (42). Prepared using the general amida-
tion procedure with Z-Gly-OH (0.105 g, 0.5 mmol) to obtain a col-
J¼7.4 Hz, 2H), 1.31 (t, J¼7.4 Hz, 3H). 13C NMR (126 MHz, CDCl3)
d
152.8, 149.9, 127.8, 118.0, 54.3, 23.2, 11.5. HRMS-EI (70 eV) m/z: Mþ
orless syrup (0.118 g, 93%). 1H NMR (400 MHz, CDCl3)
d 7.42e7.28
calcd for C7H10N2O2, 154.0742; found 154.0742.
(m, 5H), 5.56 (br s, 1H), 5.13 (s, 2H), 4.15 (d, J¼4.5 Hz, 2H), 3.72 (s,
3H), 3.20 (s, 3H). Spectra were consistent with those reported
previously.37
4.5.5. Methyl 2-isopropyl-1-imidazolecarboxylate (14d). Prepared
by analogy to methyl 2-methyl-1-imidazolecarboxylate using
2-isopropylimidazole to yield a pale yellow oil (3.73 g, 89%). 1H
4. 5.13. N-Methoxy-N-methylquinoline-2-carboxamide
(43). Prepared using the general amidation procedure with qui-
naldic acid (0.087 g, 0.5 mmol) to obtain a tan solid (0.098 g, 91%).
NMR (500 MHz, CDCl3)
d
7.31 (d, J¼1.8 Hz, 1H), 6.87 (d, J¼1.7 Hz,
1H), 3.97 (s, 3H), 3.67 (hept, J¼6.8 Hz, 1H), 1.31 (d, J¼6.8 Hz, 6H). 13C
NMR (126 MHz, CDCl3)
d
156.7, 149.8, 127.6, 118.0, 54.3, 28.1, 21.2.
1H NMR (500 MHz, CDCl3)
1H), 7.86 (d, J¼8.2 Hz, 1H), 7.76 (ddd, J¼8.3, 7.0, 1.5 Hz, 1H), 7.61 (t,
J¼7.5 Hz,1H), 3.79 (s, 4H), 3.46 (s, 3H). Spectra were consistent with
those reported previously.38
d
8.25 (d, J¼8.4 Hz, 1H), 8.14 (d, J¼8.5 Hz,
HRMS-EI (70 eV) m/z: Mþ calcd for C8H12N2O2, 168.0899; found
166.0900.
4.5.6. Z-Gly-OEt (6b). Prepared using the general amidation pro-
cedure with Z-Gly-OH (0.105 g, 0.5 mmol) to obtain a colorless
4.5.14. N-Methoxy-N-methylcinnamamide (44). Prepared using the
syrup (0.106 g, 89%). 1H NMR (400 MHz, CDCl3)
d
7.40e7.28 (m, 5H),
general amidation procedure with cinnamic acid (0.074 g,
5.26 (br s,1H), 5.13 (s, 2H), 4.21 (q, J¼7.2 Hz, 2H), 4.06e3.89 (m, 2H),
1.28 (t, J¼7.2 Hz, 3H). Spectra were consistent with those reported
previously.31
0.5 mmol) to obtain
(500 MHz, CDCl3)
a
colorless oil (0.076 g, 80%). 1H NMR
7.78 (d, J¼15.6 Hz, 1H), 7.60e7.56 (m, 2H),
d
7.40e7.34 (m, 3H), 7.07 (d, J¼15.6 Hz, 1H), 3.75 (s, 3H), 3.30 (s, 3H).
Spectra were consistent with those reported previously.39
4.5.7. Z-Gly-OAllyl (6d). Prepared using the general amidation
procedure with Z-Gly-OH (0.105 g, 0.5 mmol) to obtain a colorless
Acknowledgements
syrup (0.113 g, 91%). 1H NMR (400 MHz, CDCl3)
d 7.41e7.27 (m, 6H),
5.91 (ddt, J¼19.2, 10.8, 5.8 Hz, 1H), 5.43e5.20 (m, 3H), 5.13 (s, 3H),
4.70e4.59 (m, 2H), 4.02 (d, J¼5.6 Hz, 2H). Spectra were consistent
with those reported previously.32
The authors are grateful to the NSF for financial support (CA-
REER: CHE-0643264 and predoctoral fellowship for STH) and to
SigmaeAldrich for the gift of CDI and N,O-dihydroxylamine
hydrochloride.
4.5.8. Ethyl 4-bromobenzoate (7b). Prepared using the general
esterification procedure using 4-bromobenzoic acid (0.100 g,
0.5 mmol) in DMF (1 mL) to yield a colorless syrup (0.099 g, 86%).
Supplementary data
1H NMR (500 MHz, CDCl3)
d
7.90 (d, J¼8.5 Hz, 2H), 7.57 (d, J¼8.5 Hz,
Copies of 1H spectra for 2i, 5i, 6b, 6d, 7b, 7d, 9, 14bed, 41e44,
and copies of 13C NMR for 2i, 5i, 14ced. Supplementary data as-
sociated with this article can be found, in the online version, at
2H), 4.37 (q, J¼7.1 Hz, 2H), 1.39 (t, J¼7.1 Hz, 3H). Spectra were
consistent with those reported previously.33
4.5.9. Allyl 4-bromobenzoate (7d). Prepared using the general
esterification procedure using 4-bromobenzoic acid (0.100 g,
0.5 mmol) in DMF (1 mL) to yield a pale yellow syrup (0.115 g, 95%).
References and notes
1H NMR (500 MHz, CDCl3)
d
7.92 (d, J¼8.5 Hz, 2H), 7.58 (d, J¼8.5 Hz,
1. Otera, J.; Nishikido, J. Esterification: Methods, Reactions, and Applications; Wiley-
VCH: Weinheim, 2010.
2H), 6.02 (ddt, J¼16.6, 10.9, 5.7 Hz, 1H), 5.48e5.18 (m, 2H), 4.81 (d,
2. Carbonyl activation appears to be the most common approach. Methods in-
clude: (a) Fischer, E.; Speier, A. Chem. Ber. 1895, 28, 3252; (b) DCC/DMAP:
Hassner, A.; Alexanian, V. Tetrahedron Lett. 1978, 19, 4475; (c) ‘Mixed anhydride
method’: Kim, S.; Kim, Y. C.; Lee, J. I. Tetrahedron Lett. 1983, 24, 3365; (d) Mit-
sunobu (and references therein): Mitsunobu, O. Synthesis 1981, 1; (e) BOPCl:
J¼5.6, 2H). Spectra were consistent with those reported previously.34
4.5.10. (R)-Naproxen methyl ester (9). (R)-Naproxen (0.349 g,
1.52 mmol) was dissolved in MeOH (10 mL) and then concentrated
sulfuric acid (0.1 mL) was added dropwise. The resulting solution
was heated to 60 ꢀC for 12 h and then cooled to room temperature.
K2CO3 (0.50 g) was added and the heterogeneous mixture was
stirred for 5 min and then diluted with Et2O (50 mL). The mixture
was filtered and the filtrate was concentrated in vacuo to afford the
title compound as a white solid (0.330 g, 89%). 1H NMR (500 MHz,
ꢀ
Diago-Meseguer, J.; Palomo-Coll, A. L.; Fernandez-Lizarbe, J. R.; Zugaza-Bilbao,
€
€
A. Synthesis 1980, 547; (f) DMFDMA: Brechbuhler, H.; Buchi, H.; Hatz, E.;
Schreiber, J.; Eschenmoser, A. Helv. Chim. Acta 1965, 48, 1746; (g) Yamaugchi:
Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M. Bull. Chem. Soc. Jpn.
1979, 52, 1989; (h) EEDQ: Zacharie, B.; Connolly, T. P.; Penny, C. L. J Org. Chem.
1995, 60, 7072.
3. Methods include: (a) MeI/Cs2CO3: Pfeffer, P. E.; Silbert, L. S. J. Org. Chem. 1976,
41, 1373; (b) Me2CO3/K2CO3: Jiang, X.; Tiwari, A.; Thompson, M.; Chen, Z.;
Cleary, T. P.; Lee, T. B. K. Org. Process Res. Dev. 2001, 5, 604; (c) Me2SO4/LiOH:
Chakraborti, A. K.; Basak (nee Nandi), A.; Grover, V. J. Org. Chem. 1999, 64, 8014;
(d) Me3OBF4/DIPEA: Raber, D. J.; Gariano, P.; Brod, A. O.; Gariano, A.; Guida, W.
C.; Guida, A. R.; Herbst, M. D. J. Org. Chem. 1979, 44, 1149.
4. Kreevoy, M. M.; Thomas, S. J. J. Org. Chem. 1977, 42, 3979.
5. Mathias, L. J. Synthesis 1979, 561 and references therein.
ꢀ
CDCl3)
d
7.75e7.71 (m, 2H), 7.69 (s, 1H), 7.43 (dd, J¼8.5, 2.1 Hz, 1H),
7.17 (dd, J¼8.5, 2.1 Hz, 1H), 7.13 (s, 1H), 3.97e3.85 (m, 4H), 3.69 (s,
3H), 1.61 (d, J¼7.1 Hz, 2H). Spectra were consistent with those re-
ported previously.35 HPLC (99:1 hexanes/2-propanol), 1.0 mL/min,