S. Brass et al. / Journal of Organometallic Chemistry 691 (2006) 5406–5422
5419
DCM were added 29 dissolved in a 1:1 mixture of THF
and DCM (0.743 g, 2.00 mmol, 1.0 equiv.) and DMAP
(0.012 g, 0.10 mmol, 5 mol%) followed by the addition
of DCC (0.536 g, 2.60 mmol, 1.3 equiv.) in a 1:1 mixture
of THF and DCM. The reaction mixture was stirred at
room temperature for 14 h and then carefully quenched
by addition of a saturated NaHCO3-solution. After addi-
tion of diethyl ether the layers were separated. The
organic layer was filtered and the residue was washed
three times with diethyl ether. The combined filtrates
were washed twice with brine, dried over MgSO4, fil-
tered, and concentrated under reduced pressure. Column
chromatography (hexane/t-BuOMe: 1.5:1) afforded
0.865 g (82%) of 33 as a colourless oil: 1H NMR d
8.12 (bs, 1H), 7.60 (d, 1H, J = 7.9 Hz), 7.34 (d, 1H,
J = 7.9 Hz), 7.22–7.10 (m, 3H), 5.67 (d, 1H,
J = 14.7 Hz), 4.05–3.91 (m, 3H), 3.85 (s, 3H), 3.77 (s,
2H), 3.59 (d, 0.5H, J = 12.2 Hz), 3.49 (d, 0.5H,
J = 12.8 Hz), 3.27 (dd, 1H, J = 14.1, 7.9 Hz), 2.19 (bs,
1H), 2.13–1.90 (m, 2H), 1.42 (s, 9H), 0.88 (s, 9H), 0.03
(s, 6H); 13C NMR (rotamers) d 172.0, 155.4, 155.2,
140.3, 138.9, 136.1, 127.1, 123.2, 123.1, 122.0, 121.9,
121.6, 121.5, 119.4, 118.7, 118.6, 111.23, 111.18, 107.9,
79.7, 79.5, 67.4, 67.0, 66.8, 66.4, 49.5, 49.1, 46.2, 46.0,
36.8, 36.3, 31.2, 29.3, 28.6, 28.4, 25.8, 18.3, ꢀ5.35,
ꢀ5.41; MS (ES+) m/z 546 (90, [M+NH4]+), 1075 (100,
[2M+H+NH4]+); HRMS (ES+) m/z calcd for
C29H48N3O5Si: 546.336326; found: 546.333278.
4.2.21. 3-(2-1H-Indol-3-yl-acetoxymethyl)-5-(4-propyl-
benzoyloxymethyl)-2,3,4,7-tetrahydro-azepine-1-carboxylic
acid tert-butyl ester (35a)
To a solution of 34 (0.480 g, 1.16 mmol, 1.0 equiv.), N-
ethyl diisopropylamine (0.236 mL, 1.51 mmol, 1.3 equiv.)
and a catalytic amount of DMAP in DCM at 0 ꢁC, a solu-
tion of 4-propyl-benzoyl chloride in DCM (0.214 mL,
1.28 mmol, 1.1 equiv.) was added dropwise over a period
of 30 min. The reaction mixture was allowed to slowly
reach room temperature and stirred for additional 14 h.
After careful addition of a saturated NH4Cl-solution, the
reaction mixture was extracted three times with t-BuOMe.
The combined organic layers were washed twice with brine,
dried over MgSO4, filtered, and concentrated under
reduced pressure. Column chromatography (hexane/t-
BuOMe: 1:1) gave rise to 0.395 g (61%) of 35a as colourless
1
oil: H NMR d 8.14 (s, 1H), 7.95 (d, 2H, J = 8.0 Hz), 7.59
(d, 1H, J = 8.0 Hz), 7.32 (d, 1H, J = 8.0 Hz), 7.24 (d, 2H,
J = 8.3 Hz), 7.17 (t, 1H, J = 7.4 Hz), 7.13–7.08 (m, 2H),
5.79 (s, 1H), 4.51 (s, 2H), 4.13–4.07 (m, 1H), 3.96 (dd,
2H, J = 11.0, 7.8 Hz), 3.92–3.84 (m, 1H), 3.74 (s, 2H),
3.62–3.46 (m, 1H), 3.32 (dd, 1H, J = 14.1, 7.9 Hz), 2.63
(t, 2H, J = 7.7 Hz), 2.33–2.15 (m, 2H), 2.13–2.03 (m, 1H),
1.65 (sex, 2H, J = 7.5 Hz), 1.44 (s, 9H), 0.94 (t, 3H,
J = 7.3 Hz); 13C NMR (rotamers) d 171.9, 166.3, 155.4,
155.2, 148.4, 136.04, 135.97, 134.7, 129.6, 128.5, 127.4,
127.1, 126.6, 126.1, 123.1, 122.1, 122.0, 119.5, 118.7,
111.2, 108.1, 80.0, 79.8, 69.1, 66.3, 49.2, 49.0, 46.2, 46.0,
37.9, 36.9, 36.5, 31.3, 29.8, 29.2, 28.4, 24.2, 13.7; MS
(ES+)
m/z 583 (100, [M+Na]+), 1144
(71,
[2M+H+Na]+); HRMS (ES+) m/z calcd for C33H44N3O6
4.2.20. 5-Hydroxymethyl-3-(2-1H-indol-3-yl-
acetoxymethyl)-2,3,4,7-tetrahydro-azepine-1-carboxylic
acid tert-butyl ester (34)
([M+NH4]+): 578.323012; found: 578.322479.
Compound 33 (0.633 g, 1.20 mmol, 1.0 equiv.) was
dissolved in a 30:1 mixture of THF and aqueous HCl
32% and stirred at room temperature for 40 min. After
addition of a saturated NaHCO3-solution, the reaction
mixture was extracted three times with ethyl acetate.
The combined organic layers were washed with brine,
dried over MgSO4, filtered, and concentrated under
reduced pressure. Column chromatography (hexane/t-
BuOMe: 1:4) afforded 0.424 g (85%) of 34 as a colourless
oil: 1H NMR d 8.23 (s, 1H), 7.62 (d, 1H, J = 7.8 Hz),
7.63 (d, 1H, J = 8.0 Hz), 7.20 (t, 1H, J = 7.4 Hz), 7.17
(d, 1H, J = 1.8 Hz), 7.14 (d, 1H, J = 7.2 Hz), 5.63 (t,
1H, J = 4.4 Hz), 4.08–4.01 (m, 1H), 3.97 (dd, 1H,
J = 14.8, 7.6 Hz), 3.94–3.85 (bm, 2H), 3.79 (s, 2H),
3.75 (d, 2H, J = 7.10 Hz), 3.61–3.45 (bm, 1H), 3.30
(dd, 1H, J = 14.0, 7.8 Hz), 2.30–2.18 (bs, 1H), 2.18–
2.07 (bm, 1H), 1.99 (dd, 1H, J = 15.0, 8.1 Hz), 1.58
(bs, 1H), 1.44 (s, 9H); 13C NMR d (rotamers) 172.0,
155.3, 140.5, 139.6, 136.1, 127.1, 123.31, 123.25, 122.8,
122.0, 121.9, 119.4, 118.7, 118.6, 111.3, 107.9, 79.9,
79.7, 67.6, 67.4, 66.4, 49.3, 49.2, 46.1, 36.8, 36.3, 31.3,
29.3, 29.0, 28.4; MS (ES+) m/z 437 (100, [M+Na]+),
851 (56, [2M+Na]+); HRMS (ES+) m/z calcd for
C23H31N2O5: 415.223297; found: 415.221057.
4.2.22. 3-(2-1H-Indol-3yl-acetoxymethyl)-2,3,4,7-
tetrahydro-azepine-1-carboxylic acid tert-butyl-ester (35b)
To a solution of 34 (0.843 g, 2.03 mmol, 1.0 equiv.), tri-
ethylamine (0.4 mL, 2.85 mmol, 1.4 equiv.) and a catalytic
amount of DMAP in DCM at room temperature, a solu-
tion of acetyl chloride in DCM (0.174 mL, 2.44 mmol,
1.2 equiv.) was added dropwise. The reaction mixture
was stirred for 4 h at ambient temperature. After careful
addition of a saturated NH4Cl-solution, the reaction mix-
ture was extracted three times with diethyl ether. The com-
bined organic layers were washed twice with brine, dried
over MgSO4, filtered, and concentrated under reduced
pressure. Column chromatography (hexane/t-BuOMe:
1
1:1) gave rise to 0.730 g (79%) of 35b as colourless oil: H
NMR d 8.24 (s, 1H), 7.61 (d, 1H, J = 8.0 Hz), 7.35 (pst,
1H), 7.23–7.10 (m, 3H), 5.73–5.67 (bs, 1H), 4.29 (s, 2H),
4.09–4.01 (m, 1H), 4.00–3.92 (m, 2H), 3.88–3.82 (m, 1H),
3.79 (s, 2H), 3.61–3.47 (sm, 1H), 3.34–2.95 (sm, 1H),
2.33–2.22 (bm, 1H), 2.21–2.10 (sm, 1H), 2.04 (s, 3H),
2.07–1.97 (bm, 1H), 1.44 (s, 9H); 13C NMR (rotamers) d
171.9, 170.7, 155.3, 155.2, 136.1, 135.6, 134.5, 127.1,
126.7, 126.3, 123.1, 122.1, 122.0, 119.5, 118.73, 118.65,
111.25, 111.18, 108.1, 79.9, 79.7, 68.9, 66.4, 49.0, 46.1,
46.0, 36.7, 36.3, 31.3, 29.7, 29.6, 29.2, 28.4, 28.1, 20.8;