2938
Kim and Han
J ¼ 11.7 Hz), 7.47 (1H, d, J ¼ 8.4 Hz), 8.13 (1H, br); 13C NMR (63 MHz,
CDCl3) d 14.3, 16.5, 18.9, 28.0, 28.9, 31.6, 55.8, 60.3, 60.4, 83.5, 115.1,
116.4, 120.2, 122.3, 124.5, 129.7, 135.3, 149.1, 161.9, 163.4; FTIR (KBr,
cm21): 2978, 1739, 1693, 1372, 1160; HRMS (CI) [M þ H]þ m/z calcd for
C25H35N3O4Cl 476.2316, found 476.2319.
L-6-Chlorotryptophan (8). To a solution of (3S,6R)-3-[[1-(tert-butyl-
oxycarbonyl)-6-chloro-3-indolyl]methyl]-3,6-dihydro-6-isopropyl-2,5-diethoxy-
pyrazine 7 (0.200 g, 0.420 mmol) in THF (5.3 mL) at 08C was added 2 N HCl
(1.7 mL) in dropwise. The reaction mixture was stirred at 08C for 30 min, and
then 2 hr at an ambient temperature. After diluting with EtOAc and drying
over Na2SO4, the solvent was removed in vacuo. The crude residue was
subjected to the next step without further purification. Thus, the residue was
dissolved in saturated HCl in EtOAc (2.1 mL) at 08C and then stirred for
3 hr. After this time, the reaction mixture was concentrated. The residue
was triturated with n-hexane and the resulting solid was purified by recrystal-
lization in ether/methanol to give 0.100 g of L-6-chlorotryptophan ethyl ester
(71% for two steps) as a solid: Rf 0.26 (CH2Cl2 : MeOH, 8 : 1); [a]2D5 ¼ 12.7
1
(c 1.1, MeOH); H NMR (250 MHz, CD3OD) d 1.22 (3H, t, J ¼ 7.1 Hz),
3.35 (2H, m), 4.23 (2H, q, J ¼ 7.1 Hz), 4.37 (1H, t, J ¼ 6.7 Hz), 7.25 (1H,
dd, J1 ¼ 8.4 Hz, J2 ¼ 1.9 Hz), 7.55 (1H, d, J ¼ 8.4 Hz), 7.65 (1H, s), 8.15
(1H, d, J ¼ 1.8 Hz); 13C NMR (63 MHz, CD3OD) d 14.2, 27.4, 54.6, 63.6,
108.0, 112.4, 120.1, 120.7, 126.7, 127.0, 128.8, 138.6, 170.3; FTIR (KBr,
cm21): 2987, 1743, 1442, 1237.
To a solution of L-6-chlorotryptophan ethyl ester (0.500g, 1.48mmol) in
EtOH (7.4mL) was added 1 N NaOH (4.9mL) at 08C. The reaction mixture
was stirred for 1 hr at 408C and then brought to pH 6–8 with 5% aqueous
HCl at 08C. After removal of EtOH, the residue was diluted with H2O
and then precipitate was filtered and dried to give 0.340 g of product 8 (96%)
as a white solid: mp 242–2438C dec.; Rf 0.18 (CH2Cl2 : MeOH, 2 : 1);
1
[a]2D5 ¼ 2 9.4 (c 1.7, MeOH); H NMR (250MHz, CD3OD) d 3.16 (1H, dd,
J1 ¼ 15.2Hz, J2 ¼ 9.0 Hz), 3.47 (1H, dd, J1 ¼ 15.3Hz, J2 ¼ 3.8 Hz), 3.83
(1H, dd, J1 ¼ 9.0 Hz, J2 ¼ 4.1 Hz), 7.01 (1H, dd, J1 ¼ 8.5 Hz, J2 ¼ 1.8 Hz),
7.23 (1H, s), 7.37 (1H, d, J ¼ 1.7 Hz), 7.66 (1H, d, J ¼ 8.5 Hz); 13C NMR
(63 MHz, CD3OD) d 28.3, 56.5, 109.9, 112.2, 120.5, 120.6, 126.2, 127.2,
128.6, 138.7, 174.5; FTIR (KBr, cm21): 3397, 3061, 1665, 1590, 1453, 1353;
FABHRMS [M þ H]þ m/z calcd for C11H12N2O2Cl 239.0587, found 239.0593.
N-Trityl-6-chloro-L-tryptophan tert-butyl ester (9). To a solution of
6-chloro-L-tryptophan 8 (4.40 g, 18.5 mmol) in EtOAc (62.0 mL) was added
TMS-Cl (2.6 mL, 20.4 mmol) at 408C. The reaction mixture was stirred at
408C for 4 hr and then was cooled to room temperature. To this solution
were added NEt3 (9.4 mL, 66.7 mmol) and TrCl (5.70 g, 20.4 mmol) and
then stirred for 12 hr at 408C. The reaction mixture was washed with 5%