S. V. Andurkar et al. / Tetrahedron: Asymmetry 9 (1998) 3841–3854
3847
+
+
3
3
8
29 (M +1, 100), 285 (81), 221 (15), 286 (12); M (+CI) 329.15020 [M +1] (calcd for C H N O
r
18 21
2
4
29.15013); anal. calcd C H N O C 65.85%, H 6.10%, N 8.54%; found C 65.87%, H 6.22%, N
18
20
2
4
.47%.
4.2. (R)-N-Benzyl-2-N-(benzyloxycarbonyl)amino-3-methoxypropionamide ((R)-9)
To a CH CN solution (50 mL) of (R)-8 (1.60 g, 4.9 mmol) was successively added Ag O (7.20 g, 24.4
3
2
mmol) and MeI (4.0 mL, 49 mmol) at room temperature, and then the reaction mixture was stirred at
room temperature (3 days). The insoluble salts were filtered and the solvent was evaporated in vacuo.
The residue was purified by column chromatography (SiO , 5% MeOH–CHCl ) to obtain (R)-9 as
2
3
23
a white crystalline solid (1.40 g, 84%): mp 128–130°C; [α]D =+2.8 (c=1.1, MeOH); R 0.77 (10%
MeOH–CHCl ); IR (KBr) 3294, 2880, 1688, 1641, 1534, 1458, 1397, 1314, 1233, 1128, 1054, 964, 755,
99 cm ; H NMR (CDCl ) δ 3.37 (s, OCH ), 3.50 (dd, J=2.7, 9.3 Hz, CHH OCH ), 3.87 (dd, J=3.9,
.3 Hz, CHH OCH ), 4.35–4.40 (m, CH), 4.49 (d, J=6.0 Hz, NHCH ), 5.13 (s, C(O)OCH ), 5.65–5.75
f
3
−
1
1
0
6
9
(
5
3
3
3
0
3
2
2
13
m, NH), 6.67–6.70 (m, NH), 7.22–7.45 (m, 10 PhH); C NMR (CDCl ) 43.7 (CH NH), 54.5 (CH),
3
2
0 00 0 0
9.3 (OCH ), 67.4 (C(O)OCH ), 72.2 (CH OCH ), 127.6 (C and C4 ), 128.3 (2C2 or 2C or 2C2
3 2 2 3 4 3
00
0
00
0
0
00
00
0
0
00
00
or 2C3 ), 128.5 (2C or 2C or 2C2 or 2C3 ), 128.8 (2C2 or 2C3 or 2C2 or 2C3 ), 128.9 (2C2
or 2C3 or 2C2 or 2C3 ), 136.2 (C1 or C1 ), 138.0 (C1 or C1 ), 156.3 (C(O)O), 170.0 (C(O)NH)
ppm; MS (+CI) (rel. intensity) 343 (M +1, 100), 299 (40), 235 (31); M (+CI) 343.16681 [M +1] (calcd
2
3
0
00
00
0
00
0
00
+
+
r
for C H N O 343.16578); anal. calcd C H N O ·0.25H O C 65.80%, H 6.49%, N 8.08%; found C
19
23
2
4
19 22
2
4
2
65.67%, H 6.49%, N 8.06%.
4.3. (R)-N-Benzyl-2-amino-3-methoxypropionamide ((R)-3)
A MeOH (50 mL) solution of (R)-9 (1.00 g, 2.9 mmol) was hydrogenated in the presence of 10% Pd–C
0.20 g) at room temperature (3 h). The mixture was filtered through Celite and the clear filtrate was
evaporated in vacuo to obtain a pale yellow oil, which was purified by column chromatography (SiO ,
(
2
2
3
1
0% MeOH–CHCl ) to obtain (R)-3 (0.61 g, 100%) as a pale yellow oil: [α] =−2.0 (c=1.5, MeOH);
3
D
R 0.34 (10% MeOH–CHCl ); IR (liquid film) 3352, 3311, 3064, 2927, 2826, 1655, 1527, 1455, 1360,
f
3
−
1 1
1
251, 1181, 1106, 971, 734, 700 cm ; H NMR (CDCl ) δ 1.85 (br s, NH ), 3.34 (s, OCH ), 3.56–3.62
m, CHOCH ), 4.39 (dd, J=6.0, 15.2 Hz, NHCHH ), 4.45 (dd, J=6.0, 15.2 Hz, NHCHH ), 7.20–7.36
m, 10 PhH), 7.80–7.88 (m, NH); C NMR (CDCl ) 43.1 (NHCH ), 54.9 (CH), 58.9 (OCH ), 74.6
CH OCH ), 127.4 (C ), 127.6 (2C or 2C ), 128.6 (2C or 2C ), 138.4 (C ), 172.8 (C(O)) ppm;
3
2
3
0
0
(
(
(
2
13
3
2
3
0
0
0
0
0
0
2
3
4
2
3
2
3
1
+
+
MS (+CI) 209 (M +1); M (+CI) 209.12919 [M +1] (calcd for C H N O 209.12900); anal. calcd
r
11 17
2
2
C H N O ·0.15H O C 62.65%, H 7.74%, N 13.29%; found C 62.60%, H 7.78%, N 13.17%.
11
16
2
2
2
4
.4. (R)-N-Benzyl-2-acetamido-3-methoxypropionamide10 ((R)-2). Determination of the enantiomeric
purity of (R)-3
To a solution of (R)-3 (0.06 g, 0.3 mmol) in dry THF (3 mL) was added successively pyridine (0.02
mL, 0.3 mmol), DMAP (∼0.005 g), and Ac O (0.03 mL, 0.3 mmol), and the resulting solution was
2
stirred at room temperature (1 h). The solvents were evaporated in vacuo and the residue was purified
by PTLC (SiO , 5% MeOH–CHCl ) to obtain (R)-2 (0.07 g, 90%) as a white solid: mp 142–143°C
2
3
10
23
10
23
(
lit. mp 143–144°C); [α]D =+16.2 (c=1, MeOH) (lit. [α]D =+16.0 (c=1, MeOH)); R 0.47 (10%
f
1
MeOH–CHCl ); H NMR (CDCl ) δ 2.05 (s, C(O)CH ), 3.39 (s, OCH ), 3.45 (dd, J=7.8, 9.0 Hz,
3
3
3
3
0
0
CHH OCH ), 3.83 (dd, J=4.2, 9.0 Hz, CHH OCH ), 4.49 (d, J=5.7 Hz, NHCH ), 4.53–4.59 (m, CH),
3
3
2