Table 4.
1H NMR assignments for intermediates of ezetimibe and desfluoro ezetimibe impurity.
| Positiona |
δ ppm |
|||||
|---|---|---|---|---|---|---|
| Eze-5b | Desfluoro Eze-5b | Eze-6b | Desfluoro Eze-6b | Eze-7b | Desfluoro Eze-7b | |
| 2 | 4.19 (dd, J=8.7, 3.6 Hz, 1H) | 4.14–4.17 (m, 1H) | 4.18 (dd, J=8.7, 3.3 Hz, 1H) | 4.15 (dd, J=8.7, 3.6 Hz, 1H) | 4.24 (dd, J=8.7, 3.3 Hz, 1H) | 4.26 (dt, J=8.4, 3.0 Hz, 1H) |
| 3 | 1.79–1.90 (m, 1H); 2.16–2.28 (m, 1H) | 1.85–1.96 (m, 1H); 2.19–2.30 (m, 1H) | 1.45–1.54 (m, 1H); 1.58–1.82 (m, 1H) | 1.48–1.60 (m, 1H); 1.61–1.81 (m, 1H) | 1.44–1.53 (m, 1H); 1.58–1.74 (m, 1H) | 1.42–1.59 (m, 1H); 1.60–1.78 (m, 1H) |
| 4 | 2.90 (dt, J=7.1, 1.2 Hz, 2H) | 2.85–2.97 (m, 2H) | 1.58–1.82 (m, 2H) | 1.61–1.81 (m, 2H) | 1.58–1.74 (m, 2H) | 1.60–1.78 (m, 2H) |
| 5 | – | – | 4.51–4.60 (m, 1H) | 4.51–4.59 (m, 1H) | 4.54 (t, J=5.7 Hz, 1H) | 4.50–4.62 (m, 1H) |
| 7 | 7.88 (dd, J=8.7, 5.4 Hz, 2H) | 7.86–7.90 (m, 2H) | 7.16–7.27 (m, 2H) | 6.96–7.08 (m, 2H) | 7.04 (t, J=8.7 Hz, 2H) | 7.12–7.21 (m, 2H) |
| 8 | 6.75 (t, J=8.7 Hz, 2H) | 6.96–7.19 (m, 2H) | 6.76 (t, J=8.7 Hz, 2H) | 6.96–7.08 (m, 2H) | 6.83 (t, J=8.7 Hz, 2H) | 7.06 (dt, J=8.4, 2.4 Hz, 2H) |
| 10 | 5.06 (d, J=9.9 Hz, 1H) | 5.18 (d, J=8.1 Hz, 1H) | 5.05 (d, J=10.2 Hz, 1H) | 5.21 (d, J=9.9 Hz, 1H) | 5.08 (d, J=9.9 Hz, 1H) | 5.27 (d, J=7.8 Hz, 1H) |
| 11 | 4.47 (t, J=8.7 Hz, 1H) | 4.55–4.66 (m, 1H) | 4.40 (t, J=9.3 Hz, 1H) | 4.49 (t, J=7.8 Hz, 1H) | 4.44 (t, J=9.9 Hz, 1H) | 4.73 (t, J=8.4, 2.4 Hz, 1H) |
| 13 | 7.37–7.46 (m, 2H) | 7.38–7.43 (m, 2H) | 7.39–7.48 (m, 2H) | 7.36–7.49 (m, 2H) | 7.44–7.54 (m, 2H) | 7.47–7.56 (m, 2H) |
| 14 | 7.02–7.26 (m, 2H) | 6.96–7.19 (m, 2H) | 7.01 (t, J=8.7 Hz, 2H) | 7.16–7.25 (m, 2H) | 7.09–7.27 (m, 2H) | 7.23–7.28 (m, 2H) |
| 18 | 7.37–7.46 (m, 2H) | 6.47 (d, J=6.9 Hz, 2H) | 7.39–7.48 (m, 2H) | 6.44 (d, J=7.8 Hz, 2H) | 7.44–7.54 (m, 2H) | 6.55 (d, J=6.6 Hz, 2H) |
| 19 | 6.38 (dd, J=8.7, 4.2 Hz, 2H) | 6.61–6.68 (m, 2H) | 6.38 (dd, J=9.0, 4.5 Hz, 2H) | 6.96–7.08 (m, 2H) | 6.45 (dd, J=9.0, 4.5 Hz, 2H) | 7.12–7.21 (m, 2H) |
| 20 | – | 6.96–7.19 (m, 1H) | – | 6.63 (t, J=7.2 Hz, 1H) | – | 6.73 (t, J=7.5 Hz, 1H) |
| 21 | 5.27 (s, 2H) | 5.27 (s, 2H) | 5.28 (s, 2H) | 5.26 (s, 2H) | 5.34 (s, 2H) | 5.36 (s, 2H) |
| 23–25 | 7.02–7.26 (m, 5H) | 6.96–7.19 (m, 5H) | 7.05–7.12 (m, 5H) | 6.96–7.08 (m, 5H) | 7.09–7.27 (m, 5H) | 7.12–7.21 (m, 5H) |
| 27 | 4.55–4.62 (m, 1H); 4.67 (t, J=8.7 Hz, 1H) | 4.55–4.66 (m, 2H) | 4.51–4.60 (m, 1H); 4.64 (t, J=8.7 Hz, 1H) | 4.51–4.59 (m, 1H); 4.62 (t, J=8.7 Hz, 1H) | 4.54 (t, J=5.7 Hz, 1H); 4.69 (t, J=8.7 Hz, 1H) | 4.50–4.62 (m, 2H) |
| 28 | 5.44 (dd, J=8.4, 3.3 Hz, 1H) | 5.41 (m, 1H) | 5.40 (dd, J=8.1, 1.8 Hz, 1H) | 5.37 (dd, J=8.1, 2.7 Hz, 1H) | 5.45 (dd, J=8.4, 2.4 Hz, 1H) | 5.47 (d, J=8.1 Hz, 1H) |
| 30 | 7.02–7.26 (m, 5H) | 7.38–7.43 (m, 2H) | 7.16–7.27 (m, 4H) | 7.36–7.49 (m, 2H) | 7.33 (d, J=8.7 Hz, 2H) | 7.47–7.56 (m, 2H) |
| 31 | 7.24–7.28 (m, 2H) | 7.16–7.25 (m, 2H) | 7.09–7.27 (m, 3H) | 7.34–7.37 (m, 2H) | ||
| 32 | 6.96–7.19 (m, 1H) | 7.05–7.12 (m, 1H) | 7.13 (dt, J=7.2, 2.1 Hz, 1H) | 7.12–7.21 (m, 1H) | ||
| 33 | – | – | 2.15 (d, J=3.3 Hz, 1H) | 2.04 (d, J=2.4 Hz, 1H) | 0.00 (s, 9H) | 0.01 (s, 9H) |
Assignments: s: singlet; d: doublet; t: triplet; m: multiplet; br: broad singlet. Mean values used for coupled signals.
a
Numbering of all compounds shown in Fig. 2 and copies of NMR spectra are presented in Appendix A.
b
Solvent is CDCl3.