M.; Snead, D. R.; Stelzer, T.; Weeranoppanant, N.; Wong, S. Y.;
Zhang, P. Science 2016, 352 (6281), 61.
Lévesque, F.; Seeberger, P. H. Angew. Chem. Int. Ed. 2012, 51 (7),
1706.
Hopkin, M. D.; Baxendale, I. R.; Ley, S. V. Org. Biomol. Chem.
2013, 11 (11), 1822.
Correia, C. A.; Gilmore, K.; McQuade, D. T.; Seeberger, P. H.
Angew. Chem. Int. Ed. 2015, 54 (16), 4945.
Viviano, M.; Glasnov, T. N.; Reichart, B.; Tekautz, G.; Kappe, C.
O. Org. Process Res. Dev. 2011, 15 (4), 858.
Zhang, P.; Russell, M. G.; Jamison, T. F. Org. Process Res. Dev.
2014, 18 (11), 1567.
prevent elimination/degradation. The organic stream was
concentrated in vacuo. A mixture of 2:10:11 was obtained (1H
NMR ratio 1:0.95:0.72) 332 mg total mass, 22% yield of 2. The
aqueous stream was extracted with DCM, concentrated in vacuo.
(20)
(21)
(22)
(23)
(24)
(25)
(26)
(27)
Atropine 2 was obtained in 176 mg, 22% yield. 1H NMR and 13
C
NMR in CDCl3 are in accordance with reported literature
values.41
Acknowledgments
Ghislieri, D.; Gilmore, K.; Seeberger, P. H. Angew. Chem. Int. Ed.
2015, 54 (2), 678.
This work was supported by the Defense Advanced Research
Project Agency (DARPA), Army Research Office under contract
number W911NF-16-0023. We thank R. Beingessner for her
advice and support. ACB thanks NSERC for a postdoctoral
fellowship. HM thanks ONO pharmaceutical Co., Ltd. for their
support.
Murray, P. R. D.; Browne, D. L.; Pastre, J. C.; Butters, C.; Guthrie,
D.; Ley, S. V. Org. Process Res. Dev. 2013, 17 (9), 1192.
Heider, P. L.; Born, S. C.; Basak, S.; Benyahia, B.; Lakerveld, R.;
Zhang, H.; Hogan, R.; Buchbinder, L.; Wolfe, A.; Mascia, S.;
Evans, J. M. B.; Jamison, T. F.; Jensen, K. F. Org. Process Res.
Dev. 2014, 18 (3), 402.
(28)
Dai, C.; Snead, D. R.; Zhang, P.; Jamison, T. F. J. Flow Chem.
2015, 5 (3), 133.
References and notes
(29)
(30)
Sternbach, L. H. Angew. Chem. Int. Ed. Engl. 1971, 10 (1), 34.
Calcaterra, N. E.; Barrow, J. C. ACS Chem. Neurosci. 2014, 5 (4),
253.
Sternbach, L. H. J. Med. Chem. 1979, 22 (1), 1.
Dimitrov, K.; Metcheva, D.; Boyadzhiev, L. Sep. Purif. Technol.
2005, 46 (1–2), 41.
(1)
(2)
Beach, E. S.; Cui, Z.; Anastas, P. T. Energy Env. Sci 2009, 2 (10),
1038.
Roschangar, F.; Sheldon, R. A.; Senanayake, C. H. Green Chem.
2015, 17 (2), 752.
Sheldon, R. A. Green Chem 2007, 9 (12), 1273.
Jimenez-Gonzalez, C.; Ponder, C. S.; Broxterman, Q. B.; Manley, J.
B. Org. Process Res. Dev. 2011, 15 (4), 912.
Trost, B. Science 1991, 254 (5037), 1471.
Vaxelaire, C.; Winter, P.; Christmann, M. Angew. Chem. Int. Ed.
2011, 50 (16), 3605.
Dach, R.; Song, J. J.; Roschangar, F.; Samstag, W.; Senanayake, C.
H. Org. Process Res. Dev. 2012, 16 (11), 1697.
Constable, D. J. C.; Curzons, A. D.; Cunningham, V. L. Green
Chem. 2002, 4 (6), 521.
(31)
(32)
(3)
(4)
(33)
Gadzikowska, M.; Grynkiewicz, G. Acta Pol. Pharm. 2002, 59 (2),
149.
(5)
(6)
(34)
(35)
(36)
(37)
Mucklow, J. C. Br. J. Clin. Pharmacol. 2000, 49 (6), 613.
Ladenburg, A. Berichte Dtsch. Chem. Ges. 1879, 12 (1), 941.
Robinson, R. J. Chem. Soc. Trans. 1917, 111 (0), 762.
Gore, V.; Joshi, R.; Jadhav, M.; Bhandari, S. US Patent
2014/102829 Al, 2014.
Hilal, S. H.; Karickhoff, S. W.; Carreira, L. A. Quant. Struct.-Act.
Relatsh. 1995, 14 (4), 348.
Hilal, S. H.; Karickhoff, S. W.; Carreira, L. A. QSAR Comb. Sci.
2004, 23 (9), 709.
Trissel, L. A.; American Pharmacists Association. Trissel’s stability
(7)
(8)
(38)
(39)
(40)
(9)
Sharma, S. K. Green chemistry for environmental sustainability;
CRC Press: Boca Raton, 2010.
Kockmann, N.; Gottsponer, M.; Zimmermann, B.; Roberge, D. M.
Chem. Eur. J. 2008, 14 (25), 7470.
(10)
of compounded formulations
(11)
(12)
(13)
Malet-Sanz, L.; Susanne, F. J. Med. Chem. 2012, 55 (9), 4062.
Newman, S. G.; Jensen, K. F. Green Chem. 2013, 15 (6), 1456.
Gutmann, B.; Cantillo, D.; Kappe, C. O. Angew. Chem. Int. Ed.
2015, 54 (23), 6688.
grpalias=Alberta.
Do Pham, D. D.; Kelso, G. F.; Yang, Y.; Hearn, M. T. W. Green
Chem. 2012, 14 (4), 1189.
(41)
(14)
(15)
Pashkova, A.; Greiner, L. Chem. Ing. Tech. 2011, 83 (9), 1337.
Wegner, J.; Ceylan, S.; Kirschning, A. Chem. Commun. 2011, 47
(16), 4583.
Supplementary Material
(16)
(17)
Pastre, J. C.; Browne, D. L.; Ley, S. V. Chem. Soc. Rev. 2013, 42
(23), 8849.
Hartman, R. L.; McMullen, J. P.; Jensen, K. F. Angew. Chem. Int.
Ed. 2011, 50 (33), 7502.
Glasnov, T. N.; Kappe, C. O. Chem. Eur. J. 2011, 17 (43), 11956.
Adamo, A.; Beingessner, R. L.; Behnam, M.; Chen, J.; Jamison, T.
F.; Jensen, K. F.; Monbaliu, J.-C. M.; Myerson, A. S.; Revalor, E.
Supplementary data associated with this article can be found,
in the online version.
(18)
(19)