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Synlett 2015; 26(18): 2578-2582
DOI: 10.1055/s-0035-1560264
DOI: 10.1055/s-0035-1560264
letter
A New Microfluidic Phase-Transfer Reaction Using HPLC Guard Columns as the Reactor for the N3-Protection of Uridine Derivatives
Further Information
Publication History
Received: 13 July 2015
Accepted after revision: 12 August 2015
Publication Date:
22 September 2015 (online)
Abstract
N3-Acylation of uridine derivatives with acyl chlorides, mediated by a phase-transfer reaction, was studied using a new microfluidic device containing an HPLC guard as an effective reactor. The acylated products were obtained in more than 80% yields in very short reaction times of several seconds.
Key words
microfluidic system - phase-transfer reaction - nucleoside chemistry - flow chemistry - HPLC guard columnSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560264.
- Supporting Information
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References and Notes
- 1a Deleavey GF, Damha MJ. Chem. Biol. 2012; 19: 937
- 1b Sharma VK, Sharma RK, Singh SK. MedChemComm 2014; 5: 1454
- 1c Ma H, Liu J, Ali MM, Mahmood MA. I, Labanieh L, Lu M, Iqbal SM, Zhang Q, Zhao W, Wan Y. Chem. Soc. Rev. 2015; 44: 1240
- 2a Li J, Tan S, Kooger R, Zhang C, Zhang Y. Chem. Soc. Rev. 2014; 43: 506
- 2b Dong H, Lei J, Ding L, Wen Y, Ju H, Zhang X. Chem. Rev. 2013; 113: 6207
- 2c Navani NK, Li Y. Curr. Opin. Chem. Biol. 2006; 10: 272
- 2d Yan L, Zhou J, Zheng Y, Gamson AS, Roembke BT, Nakayama S, Sintim HO. Mol. BioSyst. 2014; 10: 970
- 3a Geary RS, Watanabe TA, Truong L, Freier S, Lesnik EA, Sioufi NB, Sasmor H, Manoharan M, Levin AA. J. Pharmacol. Exp. Ther. 2001; 296: 890
- 3b Griffey RH, Monia BP, Cummins LL, Freier S, Greig MJ, Guinosso CJ, Lesnik E, Manalili SM, Mohan V, Owens S, Ross BR, Sasmor H, Wancewicz E, Weiler K, Wheeler PD, Cook PD. J. Med. Chem. 1996; 39: 5100
- 3c Prakash TP, Kawasaki AM, Lesnik EA, Owens SR, Manoharan M. Org. Lett. 2003; 5: 403
- 3d Oeda Y, Iijima Y, Taguchi H, Ohkubo A, Seio K, Sekine M. Org. Lett. 2009; 11: 5582
- 4 Markiewicz WT. J. Chem. Res., Miniprint 1979; 173
- 5a Inoue H, Hayase Y, Imura A, Iwai S, Miura K, Ohtsuka E. Nucleic Acids Res. 1987; 15: 6131
- 5b Yamada T, Okaniwa N, Saneyoshi H, Ohkubo A, Seio K, Nagata T, Aoki Y, Takeda S, Sekine M. J. Org. Chem. 2011; 76: 3042
- 5c Saneyoshi H, Seio K, Sekine M. J. Org. Chem. 2005; 70: 10453
- 6a Beijer B, Grøtli M, Douglas ME, Sproat BS. Nucleosides Nucleotides 1994; 13: 1905
- 6b Zhou X.-X, Chattopadhyaya J. Tetrahedron 1986; 42: 5149
- 7 Sekine M. J. Org. Chem. 1989; 54: 2321
- 8 Yadav GD, Jadhav YB. J. Mol. Catal. 2003; 192: 41
- 9 Hisamoto H, Saito T, Tokeshi M, Hibara A, Kitamori T. Chem. Commun. 2001; 2662
- 10a Guillot P, Colin A. Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys. 2005; 72: 066301
- 10b Zhao Y, Chen G, Yuan Q. AIChE J. 2006; 52: 4052
- 12 Ueno M, Hisamoto H, Kitamori T, Kobayashi S. Chem. Commun. 2003; 936
- 13 Reichart B, Kappe CO, Glasnov TN. Synlett 2013; 24: 2393
- 14 Jovanović J, Rebrov EV, Nijhuis TA, Hessel V, Schouten JC. Ind. Eng. Chem. Res. 2010; 49: 2681
- 15a Yamada YM. A, Watanabe T, Torii K, Uozumi Y. Chem. Commun. 2009; 5594
- 15b Kobayashi J, Mori Y, Okamoto K, Akiyama R, Ueno M, Kitamori T, Kobayashi S. Science 2004; 304: 1305
- 15c Fukuyama T, Rahman T, Sato M, Ryu I. Synlett 2008; 151
- 15d Noël T, Musacchio AJ. Org. Lett. 2011; 13: 5180
-
16 Opalka SM, Park JK, Longstreet AR, McQuade DT. Org. Lett. 2013; 15: 996
- 17 Aota A, Hibara A, Kitamori T. Anal. Chem. 2007; 79: 3919
- 18 Hammett LP. J. Am. Chem. Soc. 1937; 59: 96
- 19 General procedure for the preparation of organic solution: 3′,5′-O-(1,1,3,3-Tetraisopropyldisiloxane-1,3-diyl)uridine (1a; 730 mg, 1.46 mmol) and an appropriate acid chloride (BzCl, AnCl, TolCl, iPrCOCl; 1.90 mmol) were dissolved in anhydrous dichloromethane (30 mL). General procedure for the preparation of aqueous solution: Sodium carbonate (4.24 g, 40 mmol) and tetrabutylammonium bromide (645 mg, 2 mmol) were dissolved in degassed H2O (200 mL). Procedure for the synthesis of 3c: The flow system was constructed as shown in Figure 1 using a guard column of monolith 2 µm (Table 1 and Table S1, entry 6). The organic solution and the aqueous solution were flowed for 15 min with the flow rate of 0.43 mL min–1 and 1.5 mL min–1, respectively. The organic solution was washed three times with saturated aqueous sodium bicarbonate and then dried over sodium sulfate. The resulting solution was evaporated under reduced pressure. The residue was dissolved in 1,2-dichloroethane (3 mL) and the solution was heated at 60 °C for 15 min. The resulting solution was evaporated under reduced pressure and then the residue was purified by column chromatography on silica gel (EtOAc–hexane, 20 to 30%) to give the product (149 mg, 69%) as a white powder. The analytical data of 3c: 1H NMR (500 MHz, CDCl3): δ = 7.88 (d, J = 8.5 Hz, 2 H), 7.78 (s, 1 H), 6.95 (d, J = 8.7 Hz, 2 H), 5.79 (d, J = 8.2 Hz, 1 H), 5.75 (s, 1 H), 4.36 (s, 1 H), 4.20 (d, J = 5.0 Hz, 2 H), 4.11 (d, J = 8.8 Hz, 1 H), 4.01 (dd, J = 13.3, 2.8 Hz, 1 H), 3.87 (s, 3 H), 2.87 (s, 1 H), 1.21–0.93 (m, 27 H); 13C NMR (126 MHz, CDCl3): δ = 167.6, 165.5, 162.4, 149.2, 139.5, 133.3, 124.3, 114.8, 102.1, 90.9, 82.3, 77.5, 77.3, 77.0, 75.4, 69.1, 60.4, 55.9, 17.7, 17.6, 17.5, 17.5, 17.3, 17.2, 17.2, 17.1, 13.6, 13.2, 13.1, 12.7; HRMS (ESI): m/z [M+Na]+ calcd for C29H44N2O9Si2Na: 643.2478; found: 643.2476. Other procedures and the analytical data are described in the Supporting Information.
- 20a Seela F, Winkeler D. Angew. Chem. Int. Ed. 1979; 18: 536
- 20b Seela F, Westermann B, Bindig U. J. Chem. Soc., Perkin Trans. 1 1988; 697
- 21 Suga S, Yamada D, Yoshida J. Chem. Lett. 2010; 39: 404