7562 J . Org. Chem., Vol. 63, No. 21, 1998
Notes
reaction mixture was filtered to remove any insoluble material
and the filtrate washed with 2 × 20 mL of 0.1 N HCl, 2 × 20
mL of 0.1 N sodium bicarbonate, and 20 mL of distilled water.
The organic phase was dried (MgSO4) and the solvent was
removed under reduced pressure. Trace amounts of DIPU were
precipitated with ether and removed by filtration. Evaporation
of the ether gave pure 15 (0.14 g, 95%): 1H NMR δ 1.49 (s, 9H),
3.97 (s, 2H); 13C NMR δ 27.84, 41.89, 82.95, 166.23.
1H NMR δ 1.00 (t, J ) 8.1 Hz, 3H), 1.28 (s, 9H), 1.51 (d, J ) 8.1
Hz, 3H), 2.11-2.16 (m, 2H), 4.47 (m, 1H), 4.51 (m, 1H), 4.98 (m,
1H), 5.23 (s, 2H), 5.32-5.70 (dd, J ) 16.2 and 86.4 Hz, 2H), 7.36
(m, 1H), 7.62 (t, J ) 8.1 Hz, 1H), 7.78 (t, J ) 8.1 Hz, 1H), 7.89
(d, J ) 8.1 Hz, 1H), 8.22 (d, J ) 8.1 Hz, 1H), 8.34 (s, 1H); 13C
NMR δ 7.52, 18.16, 28.49, 31.93, 49.75, 49.98, 67.12, 76.72, 80.23,
96.09, 120.45, 127.19, 128.09, 128.33, 128.57, 130.01, 130.40,
130.81, 145.78, 146.54, 149.27, 152.57, 155.07, 157.46, 166.88,
171.82. Anal. Calcd for C28H29N3O7: C, 64.73; H, 5.63; N, 8.08.
Found: C, 64.64; H, 5.71; N, 7.98.
Meth od B. Ca r bod iim id e P r oced u r e (Alcoh ol in Ex-
cess), Com p ou n d 16. A suspension of 1 (1.9 mL, 20 mmol),
scandium triflate (0.3 g, 0.6 mmol), 9 (0.34 g, 1 mmol), and
DMAP (0.61 g, 5 mmol) in anhydrous methylene chloride (10
mL) was cooled to -8 °C in an ice-salt bath for 30 min. 1-[3-
Com p ou n d 17: 1H NMR δ 2.14 (s, 6H), 2.37 (s, 3H), 3.47 (s,
9H), 7.00 (s, 1H); 13C NMR δ 19.18, 21.29, 41.63, 108.79, 129.33,
135.50, 142.50, 158.67, 168.14.
1
(Dimethylamino)propyl]-3-ethylcarbodiimide
hydrochloride
Com p ou n d 18: H NMR δ 1.26 (t, J ) 6.8 Hz, 3H), 1.73 (s,
(EDC; 0.38 g, 2 mmol) was added and the reaction mixture
stirred at -8 °C for 30 min and then warmed to room temper-
ature over 2 h. The reaction mixture was filtered to remove any
insoluble material, and the filtrate was washed with 2 × 20 mL
of 0.1 N HCl, 20 mL of 0.1 N sodium bicarbonate, and 20 mL of
distilled water. The organic layer was dried (MgSO4), and the
solvent was removed under reduced pressure. The product was
further purified by chromatography on a silica gel column using
0-5% methanol in methylene chloride as the eluent to give pure
16 (0.32 g, 80%): 1H NMR δ 1.25 (t, J ) 5.4 Hz, 2H), 1.43 (s,
9H), 1.46 (s, 9H), 1.95 (m, 1H), 2.10 (m, 1H), 2.46 (m, 2H), 5.12
(s, 2H), 7.35 (m, 5H); 13C NMR δ 21.71, 27.96, 28.27, 30.29, 66.44,
69.25, 77.47, 82.17, 128.23, 128.54, 135.79, 155.35, 171.63,
172.55; ESMS m/z 394 (M + H)+.
Meth od C. NHS Ester P r oced u r e (Alcoh ol in Excess),
Com p ou n d 19. A suspension of 2 (0.68 mL, 5 mmol), scandium
triflate (0.49 g, 1 mmol), and DMAP (0.73 g, 6 mmol) in
anhydrous methylene chloride (10 mL) was cooled to -8 °C in
an ice-salt bath for 30 min. Compound 12 (1.45 g, 4 mmol) was
added and the reaction mixture stirred at -8 °C for 30 min and
then warmed to room temperature over 2 h. The reaction
mixture was filtered to remove any insoluble material, the
filtrate was washed with 3 × 20 mL of 0.1 N HCl and 20 mL of
distilled water and dried (MgSO4), and the solvent evaporated.
The product was further purified by chromatography on a silica
gel column using 0-6% ethyl acetate in hexane as eluent to give
pure 19 (1.4 g, 90%): 1H NMR δ 1.25 (t, J ) 6.8 Hz, 3H), 1.42
(s, 9H), 1.51 (s, 3H), 1.55 (s, 3H), 3.02-3.20 (m, 2H), 4.14-4.27
(m, 2H), 4.55 (m, 1H), 4.92 (m, 1H), 7.21-7.30 (m, 5H); 13C NMR
δ 13.98, 24.50, 28.22, 38.17, 54.29, 61.35, 79.38, 79.77, 126.87,
128.38, 129.33, 129.48, 136.16, 155.02, 170.93, 172.04; ESMS
m/z 380 (M + H)+.
6H), 4.23 (q, J ) 5.4 Hz, 2H), 8.25 (dd, J ) 8.1 and 24.3 Hz,
4H); 13C NMR δ 13.99, 24.60, 61.54, 79.93, 123.46, 130.79,
135.53, 150.60, 163.49, 171.91; ESMS m/z 282 (M + H)+.
Com p ou n d 20: 1H NMR δ 1.43 (s, 9H), 1.65 (s, 6H), 1.95 (m,
2H), 2.10 (s, 6H), 2.17 (s, 3H), 2.44 (m, 2H), 4.20 (m, 1H), 5.05
(m, 1H), 5.12 (s, 2H), 7.35 (s, 5H); 13C NMR δ 28.17, 28.30, 30.29,
30.83, 36.03, 41.22, 53.37, 66.39, 79.72, 82.24, 128.18, 128.52,
135.84, 155.32, 170.93, 172.63; ESMS m/z 472 (M + H)+.
Com p ou n d 21: 1H NMR δ 1.42 (s, 9H), 1.64 (s, 6H), 2.05 (s,
6H), 2.17 (s, 3H), 3.05 (d, J ) 8.1 Hz, 2H), 4.45 (m, 1H), 5.00
(m, 1H), 7.16-7.29 (m, 5H); 13C NMR δ 28.30, 30.18, 30.29,
36.07, 38.53, 41.19, 54.80, 66.39, 79.56, 82.04, 126.76, 128.28,
129.56, 130.40, 155.05, 170.56; ESMS m/z 400 (M + H)+.
Com p ou n d 22: 1H NMR δ 1.41-1.47 (m, 22H), 3.08 (m, 2H),
4.52 (m, 1H), 4.96 (m, 1H), 7.18-7.29 (m, 5H); 13C NMR δ 21.94,
25.20, 28.25, 36.24, 36.75, 38.56, 54.86, 79.58, 83.65, 126.76,
128.33, 129.45, 136.45, 155.05, 170.92; ESMS m/z 362 (M + H)+.
Com p ou n d 23: 1H NMR δ 0.89 (t, J ) 8.1 Hz, 3H), 1.26 (m,
16H), 1.37 (s, 3H), 1.39 (s, 3H), 1.41 (s, 9H), 3.04 (m, 2H), 4.46
(m, 1H), 4.97 (m, 1H), 7.16-7.29 (m, 5H); 13C NMR δ 14.09,
22.66, 23.74, 25.66, 25.72, 28.28, 29.30, 29.55, 29.89, 31.87, 38.56,
41.11, 54.86, 79.58, 84.36, 126.77, 128.31, 129.48, 136.42, 155.05,
170.95; ESMS m/z 434 (M + H)+.
Com p ou n d 24: 1H NMR δ 0.88 (t, J ) 5.4 Hz, 3H), 1.26 (m,
16H), 1.37 (s, 3H), 1.41 (s, 9H), 2.51-2.53 (m, 2H), 2.99-3.06
(m, 2H), 4.47 (m, 1H), 4.96 (m, 1H), 5.04 (s, 1H), 5.08 (s, 1H),
5.61-5.71 (m, 1H), 7.17-7.31 (m, 5H); 13C NMR δ 14.08, 22.66,
23.42, 28.27, 29.29, 29.48, 29.55, 29.87, 31.87, 38.21, 38.29, 38.56,
42.67, 54.93, 79.61, 85.95, 118.39, 126.79, 128.36, 129.43, 133.08,
136.44, 155.05, 170.96; ESMS m/z 460 (M + H)+.
Com p ou n d 26: 1H NMR δ 0.92-1.02 (m, 6H), 1.26 (d, J )
5.4 Hz, 3H), 1.53 (m, 2H), 1.78 (m, 2H), 2.18-2.40 (m, 2H), 2.56
(m, 1H), 5.27 (s, 2H), 5.38-5.71 (dd, J ) 16.2, 72.9 Hz, 2H), 7.22
(m, 1H), 7.69 (t, J ) 8.1 Hz, 1H), 7.83 (t, J ) 8.1 Hz, 1H), 7.93
(d, J ) 8.1 Hz, 1H), 8.22 (d, J ) 8.1 Hz, 1H), 8.38 (s, 1H); 13C
NMR δ 7.51, 11.35, 16.18, 26.40, 31.96, 40.79, 49.88, 67.07, 75.62,
95.94, 120.56, 127.87, 128.10, 128.31, 128.60, 129.92, 130.42,
130.86, 146.25, 149.18, 152.62, 157.47, 167.24, 175.25; ESMS
m/z 433 (M + H)+.
Meth od D. NHS Ester P r oced u r e (Acid NHS Ester in
Excess), Com p ou n d 25. A suspension of 7 (0.2 g, 0.58 mmol),
scandium triflate (0.17 g, 0.35 mmol), and DMAP (0.21 g, 1.7
mmol) in anhydrous methylene chloride (5 mL) was cooled to
-8 °C using an ice-salt bath for 30 min. Compound 13 (0.50 g,
1.7 mmol) was added and the reaction mixture stirred at -8 °C
for 30 min and then warmed to room temperature over 2 h. The
reaction mixture was filtered to remove any insoluble material,
the filtrate was washed with 3 × 20 mL of 0.1 N HCl and 20
mL of distilled water and dried (MgSO4), and the solvent
removed under reduced pressure. The product was further
purified by crystallization from 2 mL of methanol (0.28 g, 94%):
Ack n ow led gm en t. We wish to thank Dr. Yun Choe
for her efforts in helping to prepare this paper.
J O981161C