Molecules 2019, 24, 1828
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3.3.6. Rimantadine (10) (S)-Aspartic Acid (18) 0.5 Eq. Salt
Mw: 0.36 g, 52.0% yield, 7.44% ee (S), mp: 205–208 ◦C. 1H NMR (400 MHz, CD3OD):
δ
= 4.69–4.79
(m, 1H), 2.75–2.93 (m, 2H), 2.49–2.63 (m, 1H), 1.98–2.09 (m, 3H), 1.45–1.90 (m, 13H), 1.18 (d, J = 6.6 Hz, 3H).
3.3.7. Rimantadine (10) (S)-Aspartic acid (18) 0.25 Eq. Salt (1:1 Salt)
Mw: 0.17 g, 24.6% yield, 7.20% ee (S), mp: 207–209 ◦C. 1H NMR (400 MHz, CD3OD):
δ = 4.67–4.78
(m, 1H), 2.76–2.91 (m, 2H), 2.48–2.61 (m, 1H), 1.98–2.09 (m, 3H), 1.50–1.90 (m, 13H), 1.15 (d, J = 6.7 Hz, 3H).
3.3.8. Rimantadine (10) (S)-Malic Acid (19) 1.0 Eq. Salt
Mw: 0.52 g, 59.2% yield, 0.20% ee (S), mp: 206–209 ◦C. 1H NMR (400 MHz, CD3OD):
δ = 4.21–4.31
(m, 1H), 2.80–2.92 (m, 2H), 2.65–2.79 (m, 1H), 2.35–2.51 (m, 1H), 1.98–2.12 (m, 6H), 1.49–1.89 (m, 27H),
1.18 (d, J = 6.7 Hz, 6H).
3.3.9. Rimantadine (10) (S)-Malic Acid (19) 0.25 Eq. Salt
Mp: 207–211 ◦C. 1H NMR (400 MHz, CD3OD):
δ = 4.21–4.31 (m, 1H), 2.78–2.92 (m, 2H), 2.65–2.79
(m, 1H), 2.39–2.51 (m, 1H), 1.97–2.10 (m, 6H), 1.51–1.88 (m, 26H), 1.18 (d, J = 6.7 Hz, 6H).
3.3.10. Rimantadine (10) N-Tosyl-(S)-proline (20) 0.5 Eq. Salt
Mw: 0.08 g, 6.4% yield, 95.46% ee (R), mp: 178–181 ◦C. 1H NMR (400 MHz, CD3OD):
δ = 7.72–7.81
(m, 2H), 3.95–4.05 (m, 1H), 3.45–3.55 (m, 2H), 3.15–3.25 (m, 1H), 2.80–2.94 (m, 1H), 2.53 (s, 3H), 2.65–2.79
(m, 1H), 2.00–2.11 (m, 3H), 1.59–1.89 (m, 15H), 1.19 (d, J = 6.6 Hz, 3H).
3.3.11. Rimantadine (10) (1R,3S)-Camphoric Acid (21) 0.5 Eq. Salt
Mw: 0.78 g, 100% yield, 0.72% ee (S), mp: 180–182 ◦C. 1H NMR (400 MHz, CD3OD):
δ = 2.70–2.90
(m, 1H), 2.42–2.70 (m, 1H), 1.98–2.11 (m, 3H), 1.60–1.88 (m, 14H), 1.45 (s, 1H), 1.35 (s, 3H), 1.18 (d, J =
6.6 Hz, 3H), 0.90 (s, 2H).
3.3.12. Rimantadine (10) (1R,3S)-Camphoric Acid (21) 0.25 Eq. Salt
Mw: 0.13 g, 16.8% yield, 0.38% ee (S), mp: 182–186 ◦C. 1H NMR (400 MHz, CD3OD):
δ = 2.70–2.85 (m,
1H), 2.52–2.70 (m, 1H), 1.97–2.12 (m, 3H), 1.55–1.88 (m, 12H), 1.38 (s, 1H), 1.14–1.22 (m, 6H), 0.90 (s, 1H).
3.3.13. Rimantadine (10) (1S)-10-Camphorsulforic Acid (22) 1.0 Eq. Salt
Mw: 0.81 g, 70.9% yield, 5.22% ee (R), mp: 204–208 ◦C. 1H NMR (400 MHz, CD3OD):
δ = 3.31–3.41
(m, 2H), 2.82 (q, J = 6.5 Hz, 1H), 2.60–2.80 (m, 2H), 2.28–2.49 (m, 1H), 2.00–2.18 (m, 5H), 1.40–1.90 (m,
16H), 1.20 (d J = 6.5 Hz, 3H), 1.15 (s, 3H), 0.89 (s, 3H).
3.3.14. Rimantadine (10) (2S,3S)-Tartaric Acid (23) 0.5 Eq. Salt
Mw: 0.73 g, 103% yield, 1.38% ee (S), mp: 220–221 ◦C. 1H NMR (400 MHz, CD3OD):
1H), 2.80 (q, J = 6.5 Hz, 1H), 1.96–2.18 (m, 3H), 1.45–1.89 (m, 12H), 1.15 (d, J = 6.5 Hz, 3H).
δ = 4.30 (s,
3.3.15. Rimantadine (10) (2S,3S)-Tartaric Acid (23) 0.25 Eq. Salt
Mw: 0.35 g, 49.0%, 23.24% ee (S), mp: 217–219 ◦C. 1H NMR (400 MHz, CD3OD):
2.81 (q, J = 6.6 Hz, 1H), 1.97–2.08 (m, 3H), 1.44–1.88 (m, 13H), 1.12 (d, J = 6.5 Hz, 3H).
δ = 4.30 (s, 1H),
3.3.16. Rimantadine (10) (2S,3S)-Dibenzoyltartaric Acid (24) 0.5 Eq. Salt (2:1 Salt)
◦
1
Mw: 0.87 g, 86.6% yield, 16.38% ee (R), mp: 168–171 C. H NMR (400 MHz, CD3OD):
δ =
8.15–8.22 (m, 2H), 7.50–7.75 (m, 3H), 5.89 (s, 1), 2.72 (q, J = 6.6 Hz, 1H), 1.91–2.08 (m, 3H), 1.42–1.89 (m,
12H), 1.11 (d, J = 6.5 Hz, 3H).