The Journal of Organic Chemistry
Article
h (creates initial seed bed). Water (150 mL) was added to the flask at 52
°C slowly over 1 h, and the slurry was agitated at this temperature for 1 h.
Water (300 mL) was added to the reaction mixture at 52 °C slowly over
1 h, the mixture was agitated at 52 °C for 2 h, and the slurry was cooled
to 20 °C linearly over 4 h and stirred at 20 °C for 9 h. The product was
collected by filtration, and the solid was rinsed consecutively with water
(150 mL), isopropyl acetate (150 mL), and heptane (150 mL). The
solid was dried for 1 h at 20 °C on the funnel and then for 24 h at 55 °C
under vacuum, giving 58.3 g of 1 as an off-white crystalline solid (94.4%
yield, 98.5 wt %, 99.8% ee). Crude 1 could be further purified by
recrystallization from ethanol/water. Mp: 196 °C. 1H NMR (DMSO-d6,
500 MHz): δ 8.55 (s, 2H), 8.49 (s, 1H), 8.06 (s, 1H), 7.56 (d, J = 8.48
Hz, 2H), 7.38 (d, J = 8.48 Hz, 2H), 6.75 (s, 2H), 5.22 (s, 2H), 3.03 (s,
3H), 2.85 (s, 3H), 1.67 (m, 1H), 0.64 (m, 1H), 0.31−0.52 (m, 3H). 13C
NMR (DMSO-d6, 125 MHz): δ 175.7, 170.4, 165.9, 162.9, 155.9, 143.8,
138.6, 134.0, 133.6, 127.4, 125.2, 121.8, 106.7, 53.2, 42.8, 35.90, 35.3,
22.1, 19.4, 2.1, 1.1. HRMS (TOF MS): [C24H26N8O2 + H+] calculated
459.2251, found 459.2241.
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S
* Supporting Information
Figures, tables, and a CIF file giving crystallographic data for
1
compound 23, H NMR, 13C NMR, and chiral HPLC spectra,
and computational data. This material is available free of charge
AUTHOR INFORMATION
Corresponding Authors
■
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1991, 56, 3286−3294. (b) Scott, H. K.; Aggarwal, V. K. Chem. Eur. J.
2011, 17, 13124−13132.
Present Addresses
†Department of Medicinal Chemistry, Boehringer-Ingelheim
Pharmaceuticals Inc., 900 Ridgebury Road, P.O. Box 368,
Ridgefield, CT 06877-0368, United States.
(13) Farina, V.; Reeves, J. T.; Senanayake, C. H.; Song, J. J. Chem. Rev.
2006, 106, 2734−2793.
‡Department of Chemical Development, Boehringer-Ingelheim
Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397
Biberach/Riß, Germany.
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Notes
The authors declare no competing financial interest.
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