172
Zhang et al.
1H), 7.16 (t, J D 7.0 Hz, 3H), 7.25–7.29 (m, 5H), 7.31–7.35 (m, 2H). 13C NMR (CDCl3) d
25.95, 26.69, 27.02, 27.94, 29.24, 29.54, 35.63, 53.70, 58.43, 62.06, 63.79, 69.11, 70.64,
70.77, 116.09, 125.16, 125.37, 125.59, 126.65, 127.22, 128.17, 128.32, 128.36, 128.96,
132.78, 138.35, 142.36, 155.43; EIMS m/z 487 ([M-H2O]C, 9), 352 (100), 91 (73), 134
(28), 353 (26) , 112 (10).
4-Hydroxy-1-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-1,3-benzenedimethanol
(Salmeterol 9) 3
Compound 8 (7.10 g, 14 mmol) was dissolved in ethanol (60.0 mL) and hydrogꢀenated at
58 psi (0.4MPa) pressure in the presence of 10% Pd-C (600 mg) for 36 h at 45 C. After
removal of the catalyst, the filtrate was concentrated in vacuo. The crude solid was recrys-
tallized from EtOAc to give 4.6 g (80%) of salmeterol (9) as a white powder, mp. 75-
3
1
ꢀ
ꢀ
76 C (lit. 75-77 C), H NMR (CDCl3): d 1.25-1.30 (m, 4H), 1.43 (t, J D 7.0 Hz, 2 H),
1.51 (dd, J D 6.5, 13.5 Hz, 2H), 1.58-1.64 (m, 2H), 1.65-1.68 (m, 2H), 3.36 (t, J D
7.0 Hz, 2H), 3.40 (t, J D 6.5 Hz, 2H), 4.50 (t, J D 6.5 Hz, 1H), 4.62 (s, 2H) 4.78 (s, 4H),
6.70 (d, J D 8.0 Hz, 1H), 6.89 (s, 1 H), 6.99 (d, J D 8.0 Hz, 1H), 7.15 (t, 3H, J D 7.5 Hz),
7.25 (q, J D 6.5 Hz, 3H). 13C NMR (CDCl3) d 26.01, 27.04, 27.99, 29.30, 29.43, 29.59,
35.68, 49.29, 56.55, 62.98, 70.72, 70.83, 71.42, 116.21, 125.65, 126.11, 126.39, 128.23,
128.37, 133.50, 142.42, 155.63; EIMS m/z 397 ([M-H2O] C,10), 112 (100), 91 (64), 262
(36), 114 (28), 116 (23).
Acknowledgment
We are grateful to the National Natural Science Foundation of China (No. 21372203 and
21272076) and Zhejiang Apeloa Pharmaceutical Co., Ltd.
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