U. Jacquemard et al. / Tetrahedron 60 (2004) 10039–10047
10045
(20 mL) was added and the aqueous phase was extracted
with CH2Cl2 (3!20 mL). The combined organic layers
were dried over MgSO4, filtered and the solvent was
removed under reduced pressure. The crude product was
purified by flash chromatography (petroleum ether/EtOAc
8/2) to afford compound 30 as a white solid (698 mg, 85%).
Mp 74 8C; Rf (petroleum ether/EtOAc 8/2): 0.15; IR (KBr,
cmK1) n 3321, 3050, 2950, 2882, 1707, 1537, 1493, 1292,
1249, 1205; 1H NMR (CDCl3) d 2.85 (t, 2H, JZ7 Hz), 3.52
(q, 2H, JZ6.5 Hz), 5.1 (bs, 1H), 7.04–7.41 (m, 8H); 13C
NMR (CDCl3) d?35.1 (CH2), 42.0 (CH2), 121.5 (2CH),
125.4 (CH), 128.2 (CH), 129.3 (2CH), 130.6 (CH), 130.7
(CH), 132.5 (Cq), 138.8 (Cq), 150.8 (Cq), 154.5 (Cq); MS
(IS) 310/312 (MCH)C, 332/334 (MCNa)C. HRMS-EI
(MC): 309.03233 calcd for C15H13Cl2NO2, found 309.0318.
3543 (559 mg, 2.15 mmol), phenyl chloroformate
(0.432 mL, 3.44 mmol) in CH2Cl2 containing NaOH
(258 mg, 6.45 mmol) and a catalytic amount of tetrabutyl
ammonium bromide (21 mg, 0.06 mmol) was stirred at rt
under argon. After 12 h water (20 mL) was added and the
aqueous phase was extracted with EtOAc (3!20 mL). The
combined organic layers were dried over MgSO4, filtered
and the solvent was removed under reduced pressure. The
crude product was purified by flash chromatography
(petroleum ether then petroleum ether/EtOAc 8/2) to afford
compound 33 as a white solid (579 mg, 71%). Mp 132 8C;
Rf (petroleum ether/EtOAc 7/3):0.68; IR (KBr, cmK1) n
3306, 3053, 3004, 2977, 2899, 1754, 1692, 1535, 1457,
1
1383; H NMR (CDCl3) d: 1.44 (s, 9H), 2.92 (t, 2H, JZ
6.6 Hz), 3.48 (q, 2H, JZ6.3 Hz), 4.76 (bs, 1H), 7.23–7.47
(m, 6H), 7.57–7.59 (m, 2H), 8.22 (bd, 1H, JZ7.5 Hz); 13C
NMR (CDCl3) d: 25.6 (CH2), 28.3 (3CH3), 40.0 (CH2), 79.2
(Cq), 115.3 (CH), 119.1 (CH), 119.5 (Cq), 121.4 (2CH),
122.6 (CH), 123.2 (CH), 125.0 (CH), 126.3 (CH), 129.5
(2CH), 130.6 (Cq), 135.7 (Cq), 149.0 (Cq), 150.2 (Cq),
155.8 (Cq); MS (IS) 281 (MCHKBoc)C, 381 (MCH)C,
398 (MCNH4)C. HRMS-ESI (MCNaC): 403.16338 calcd
for C22H24N2O4Na, found 403.1635.
4.1.4. [2-(3,4-Dichloro-phenyl)-ethyl]-carbamic acid tert-
butyl ester (31). A solution of 3,4-dichlorophenylethyla-
mine 29 (500 mg, 2.64 mmol), 4-DMAP (322 mg
2.64 mmol) and Boc2O (690 mg, 3.16 mmol) in acetonitrile
(15 mL) was stirred at rt under argon. After 4 h, water
(20 mL) was added and the aqueous phase was extracted
with EtOAc (3!20 mL). The combined organic layers were
dried over MgSO4, filtered and the solvent was removed
under reduced pressure. The crude product was purified by
flash chromatography (petroleum ether then petroleum
ether/ EtOAc 6/4) to afford compound 31 as white solid
(762 mg, quant.). Mp 86 8C. Rf (petroleum ether/EtOAc 5/
5): 0.54; IR (KBr, cmK1) n 3338, 2979, 2925, 1687, 1534,
4.1.7. 3-(2-Phenoxycarbonylamino-ethyl)-indole-1-car-
boxylic acid tert-butyl ester (34). A solution of 3-(2-
phenoxycarbonylamino-ethyl)-indole40 (150 mg, 0.53 mmol)
in a mixture of THF (2 mL) and DMF (2 mL) was treated
with 4-(dimethylamino)pyridine (6 mg, 0.05 mmol),
triethylamine (74 mL, 0.53 mmol) and di-tert-butyl dicarbo-
nate (128 mg, 0.59 mmol). Stirring was continued over-
night. After addition of water (20 mL), the crude product
was extracted with ethyl acetate (2!10 mL). The combined
organic layers were then washed twice with brine.
Purification of the crude product by flash chromatography
(petroleum ether/EtOAc 8/2) afforded compound 34
(104 mg, 51%). Colorless oil; Rf (petroleum ether/EtOAc
6/4):0.88; IR (NaCl, cmK1) n 3355, 2974, 2940, 1731, 1527,
1
1283, 1168; H NMR (CDCl3) d: 1.44 (s, 9H), 2.79 (t, 2H,
JZ6.7 Hz), 3.39 (m, 2H), 4.57 (s, 1H), 7.02 (d, 1H, JZ
8.3 Hz), 7.29 (s, 1H), 7.36 (d, 1H, JZ8.3 Hz); 13C NMR
(CDCl3) d 28.7 (CH3), 35.7 (CH2), 41.8 (CH2), 79.9 (Cq),
128.6 (CH), 130.8 (CH), 131.2 (CH), 132.8 (Cq), 139.6
(Cq), 156.2 (Cq); MS (IS) 290/292 (MCH)C. HRMS-ESI
(MCNaC): 312.05340 calcd for C13H17NO2Cl2Na, found
312.0539.
1
1491, 1454, 1256, 1207, 1159, 1091; H NMR (CDCl3) d:
4.1.5. 3-(2-tert-Butoxycarbonylamino-ethyl)-indole-1-
carboxylic acid tert-butyl ester (32). A solution of
tryptamine hydrochloride (1.38 g, 7.57 mmol), 4-DMAP
(1.11 g, 9.08 mmol) and Boc2O (3.46 g, 15.89 mmol) in
acetonitrile (20 mL) was stirred at rt under argon. After
12 h, water (50 mL) was added and the aqueous phase was
extracted with EtOAc (3!50 mL). The combined organic
layers were dried over MgSO4, filtered and the solvent was
removed under reduced pressure. The crude product was
purified by flash chromatography (petroleum ether then
petroleum ether/ EtOAc 8/2) to afford compound 32 as a
waxy solid (2.45 g, 90%). Rf (petroleum ether/EtOAc 9/1):
0.24; IR (KBr, cmK1) n 3374, 2976, 2930, 1724, 1722, 1545,
1254, 1160, 1091; 1H NMR (CDCl3) d: 1.44 (s, 9H), 1.66 (s,
9H), 2.89 (t, 2H, JZ7.0 Hz), 3.46 (m, 2H), 4.63 (s, 1H),
7.23 (m, 2H), 7.41 (s, 1H), 7.53 (d, 1H, JZ7.8 Hz), 8.13 (d,
1H, JZ8.0 Hz); 13C NMR (CDCl3) d 26.0 (CH2), 28.6
(CH3), 28.8 (CH3), 40.7 (CH2), 79.5 (Cq), 83.8 (CH3), 115.7
(CH), 118.2 (Cq), 119.4 (CH), 122.8 (CH), 123.5 (CH),
124.8 (CH), 130.8 (Cq), 135.9 (Cq), 150.1 (Cq), 156.4 (Cq);
MS (IS) 361 (MCH)C. HRMS-ESI (MCNaC): 383.19468
calcd for C20H28N2O4Na, found 383.1948.
1.67 (s, 9H), 2.99 (t, 2H, JZ6.8 Hz), 3.60 (q, 2H, JZ
6.6 Hz), 5.14 (bs, 1H), 7.09–7.38 (m, 6H), 7.46 (s, 1H), 7.58
(d, 1H, JZ7.6 Hz), 8.14 (bd, 1H, JZ7.6 Hz); 13C NMR
(CDCl3) d: 25.0 (CH2), 27.8 (CH3!3), 40.6 (CH2), 83.2
(Cq), 115.0 (CH), 117.3 (Cq), 118.7 (CH), 121.3 (CH!2),
122.2 (CH), 122.8 (CH), 124.2 (CH), 124.9 (CH), 128.9
(CH!2), 130.1 (Cq), 135.2 (Cq), 149.4 (Cq), 150.8 (Cq),
154.5 (Cq); MS (IS) 381 (MCH)C, 403 (MCNa)C.
HRMS-ESI 403.16338
C22H24N2O4Na, found 403.1635.
(MCNaC):
calcd
for
4.1.8. 3-(2-Amino-ethyl)-indole-1-carboxylic acid tert-
butyl ester (36). A solution of 34 (89 mg, 0.234 mmol)
and TBAF (0.28 mL, 1 M in THF, 0.281 mmol) in dry THF
(2.5 mL) was stirred under argon at rt. After 30 min water
(5 mL) was added and the aqueous phase was extracted with
EtOAc (3!5 mL). The combined organic layers were dried
over MgSO4, filtered and the solvent was removed under
reduced pressure. The crude product was purified by flash
chromatography (CH2Cl2/MeOH 9/1) to afford compound
36 as colorless oil (50 mg, 83%). Rf (CH2Cl2/MeOH 9/1):
0.22; IR (NaCl, cmK1) n 3404, 2976, 2922, 1731, 1454,
1
4.1.6. 3-(2-tert-Butoxycarbonylamino-ethyl)-indole-1-
carboxylic acid phenyl ester (33). A solution of compound
1369, 1250, 1157; H NMR (CDCl3) d: 1.66 (s, 9H), 2.62
(bs, 2H), 2.89 (t, 2H, JZ6.4 Hz), 3.07 (bs, 2H), 7.23 (dd,