ACCEPTED MANUSCRIPT
(
100 MHz, CD OD)
δ
(ppm): 18.15, 22.90, 31.13, 31.50, 31.98, 35.79, 36.71, 50.61, 119.83, 123.69,
3
128.36, 138.50, 173.12, 174.72. IR: 3302, 3137, 3061, 2953, 2940, 2869, 1736, 1662, 1600, 1542,
-
1
+
+
1
499, 1442 cm . LRMS (ESI, m/z): calculated for [M+H] C H NO H , 278.18, found 278.17;
16
23
3
+
+
calculated for [M+Na] C H O Na , 300.16, found 300.10.
16
23
3
4.2.1.8. Synthesis of methyl 4-ethyl-8-oxo-8-(phenylamino)octanoate (8b): The procedure was
similar to the last step of 8a except the following reagents were used: DIPEA (319 mg, 2.47mmol),
TBTU (594 mg, 1.85 mmol) and aniline (172 mg, 185 mmol). The extraction was done with
dichloromethane (4 x 20 mL). The product was purified by silica gel flash chromatography (ethyl
1
acetate:hexanes 1:4) to afford 8b (250 mg, 75%). HNMR (400 MHz, CD OD)
δ (ppm): 0.87 (t, J = 7.2
3
Hz, 3H), 1.34 (m, 5H), 1.60 (m, 2H), 1.68 (m, 2H), 2.33 (m, 4H), 3.64 (s, 3H), 7.07 (t, 1H), 7.29 (t, J =
1
3
7
3
3
.2 Hz, 2H), 7.53 (d, J = 7.2 Hz, 2H). CNMR (100 MHz, CD
3
OD) δ (ppm): 9.35, 22.23, 24.83, 27.55,
0.56, 31.63, 36.48, 37.83, 50.32, 119.55, 123.40, 128.06, 138.19, 172.82, 174.49. IR: 3302, 3198, 3137,
-1
062, 2955, 2930, 2862, 1737, 1663, 1600, 1542, 1499, 1442 cm . LRMS (ESI, m/z): calculated for
+
+
+
+
[
M+H] C H O H , 292.19, found 292.19; calculated for [M+Na] C H O Na , 314.17, found 314.17.
17
25
3
I7 25
3
4.2.1.9. Synthesis of methyl 4-butyl-8-oxo-8-(phenylamino)octanoate (8c): The procedure was
similar to that of 7b except the following reagents were used: 6c (1.2 g, 3.6 mmol) Pd(OH) (504 mg
2
of 20 wt. % Pd(OH) on carbon, 0.72 mmol). The crude product was used in the following reaction.
2
The procedure was similar to the last step of 8a except the following reagents were used: Crude 7c
from prior reaction, DIPEA (464 mg, 3.59 mmol), TBTU (865 mg, 2.69 mmol) and aniline (250 mg, 2.69
mmol). The product was purified by silica gel flash chromatography (ethyl acetate:hexanes 1:6) to
1
afford 8c (250 mg, 44% over two steps). HNMR (400 MHz, CD OD)
δ
(ppm): 0.89 (t, J = 6.4 Hz,
3
3H), 1.31 (m, 9H), 1.60 (m, 2H), 1.68 (m, 2H), 2.32 (m, 4H), 2.82 (s, 3H), 7.06 (t, J = 7.2 Hz, 1H), 7.28
13
(
t, J = 8 Hz, 2H), 7.53 (d, J = 8 Hz, 2H). CNMR (100 MHz, CD OD)
δ
(ppm): 13.07, 22.48, 22.66,
3
28.29, 28.46, 30.84, 32.37, 32.55, 36.56, 36.77, 50.63, 119.84, 123.69, 128.36, 138.49, 173.10,
-
1
1
74.77. IR: 3302, 3198, 3137, 3041, 2953, 2928, 2859, 1737, 1661, 1600, 1541, 1499, 1441 cm .
+
+
+
LRMS (ESI, m/z): calculated for [M+H] C H NO H , 320.22, found 320.21; calculated for [M+Na]
19
29
3
+
C H NO Na , 342.20, found 342.17.
19
29
3
26