19F NMR monitoring of S(N)Ar reaction on solid support

Tetrahedron Letters

Volumn 37, Issue 27, 1996, Pages 4671-4674

  Shapiro, Michael J ^a   Kumaravel, G ^a   Petter, Russell C ^a   Beveridge, Richard ^a  

^a Sandoz Pharma Ltd   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS;

EID: 0030199617     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00960-4     Document Type: Article

References (17)

1. 1. March, J. Advanced Organic Chemistry, 4th Ed.; Wiley & Sons: New York, 1992; pp 641-676.
2. 2. (a) Beugelmans, R.; Zhu, J.; Husson, N; Bois-Choussy, M.; Sing, G. P. J. Chem. Soc., Chem. Commun. 1994, 439-440.
3. (b) Rama Rao, A. V.; Laxma Reddy, K.; Srinivasa Rao, A. Tetrahedron Lett. 1994, 35, 8465-8468.
4. (c) Beugelmans, R.; Singh, G. P.; Bois-Choussy, M.; Chastanet, J.; Zhu, J. J. Org. Chem. 1994, 59, 5535-5542.
5. 3. (a) Beugelmans, R.; Bourdet, S.; Zhu, J. Tetrahedron Lett. 1995, 36, 1279-1282.
6. (b) Zhu, J.; Beugelmans, R.; Bourdet, S.; Chastanet, J.; Roussi, G. J. Org. Chem. 1995, 60, 6389-6396.
7. 4. Boger, D. L; Borzilleri, J. M. Bioorg. Med. Chem. Lett. 1995, 5, 1187-1190.
8. 5. Beugelmans, R.; Bigot, A.; Zhu, J. Tetrahedron Lett. 1994, 35, 7391-7394.
9. 6. (a) Anderson, R. C.; Jarema, M. A.; Shapiro, M. J.; Stokes, J. P.; Ziliox, M. J. Org. Chem. 1995, 60, 2650.
10. (b) Anderson, R. C.; Shapiro, M. J.; Stokes, J. P. Tetrahedron Lett. 1995, 36, 5311.
11. (c) Yan, B.; Kumaravel, G.; Anjaria, H.; Wu, A.; Petter, R. C.; Jewell, C. F., Jr.; Wareing, J. R. J. Org. Chem. 1995, 60, 5736-5738.
12. 7. Fyfe, C. A. Solid State NMR for Chemists; CFC Press: Guelph, Ontario, 1983.
13. 8. (a) Manatt, S. L.; Amsden, S. F.; Bettison, C. A.; Frazer, W. T.; Gudman, J. T.; Lenk, B. E.; Lubetich, J. F.; McNelly, E. A.; Smith, S. C.; Templeton, D. J.; Pinnell, R. P. Tetrahedron Lett. 1980, 21, 1397-1400.
14. (b) Blossey E.; Cannon, R. G.; Ford, W. T.; Periyasamy, M.; Mohanraj, S. J. Org. Chem. 1990, 55, 4664-4668.
15. 1H NMR after cleavage from the resin. The NMR spectra were consistent with the expected product from nucleophilic substitution of the fluorine atom: δ = 8.4 (d, 1H), 7.6 (dd, 1H), 6.3 (d, 1H), 3.9 (q, 2H) 3.0 (t, 2H), 2.1 (t, 2H), 1.0 (t, 3H).
16. 10. For typical gel phase NMR spectra, it took 1 to 1.5 hours to acquire data sufficient to attain the signal-to-noise ratio shown in Figure 1. The sample was shown to be stable to the conditions by repeating the data acquisition for a sample sitting in solution for 4 days, obtaining the same results.
17. 6. The solvent-swollen powder was placed into a 7 mm rotor. The broad component from the probe background was removed by zeroing and linear predicting of the first 20 points of the FID. Gel-phase NMR data were obtained on a Bruker AC-300 spectrometer equipped with a 5 mm quad nucleus probe.