4714
E. Tayama et al. / Tetrahedron 68 (2012) 4710e4718
CDCl3)
d
171.2, 137.2, 135.4, 130.3, 128.2, 127.3, 125.9, 80.8, 70.9, 51.9,
NMR (400 MHz, CDCl3)
d
7.16 (1H, d, J¼1.4 Hz, ArH), 7.06 (1H, d,
27.9, 26.0, 24.6, 19.6; HRMS-ESI (m/z): [MþH]þ calcd for C18H28NO2:
J¼7.6 Hz, ArH), 7.00 (1H, dd, J¼7.6, 1.4 Hz, ArH), 4.48 (1H, s, CHCO),
3.85e3.07 (8H, m, morpholinyl-CH2), 2.72e2.64 (2H, m, piper-
idinyl-NCH2), 2.61e2.52 (2H, m, piperidinyl-NCH2), 2.38 (3H, s,
290.2115. Found: 290.2110.
3.4.4. N-tert-Butyl-2-(2-methylphenyl)-2-(piperidin-1-yl)acetamide
(5d). White solid. IR (film) 3335, 3054, 3023, 2933, 2857, 2806,
2758, 1681, 1508, 1454, 1391, 1363, 1275, 1254, 1228, 1177, 1154,
ArCH3), 2.30 (3H, s, ArCH3), 1.59e1.39 (6H, m, piperidinyl-CH2); 13
C
NMR (100 MHz, CDCl3)
d 170.5, 135.1, 134.1, 133.9, 130.6, 129.3,
128.3, 67.8, 66.8, 66.1, 51.2, 45.6, 42.0, 26.4, 24.6, 20.9, 19.0; HRMS-
1108, 1093, 1037, 992, 961, 874, 817, 788, 757, 736 cmꢀ1
;
1H NMR
ESI (m/z): [MþH]þ calcd for C19H29N2O2: 317.2224. Found: 317.2219.
(400 MHz, CDCl3)
d 7.29e7.25 (1H, m, ArH), 7.20 (1H, br, NH),
7.18e7.10 (3H, m, ArH), 4.01 (1H, s, CHCO), 2.44 (3H, s, ArCH3),
2.43e2.32 (4H, m, NCH2), 1.63e1.41 (6H, m, CH2), 1.35 (9H, s, t-Bu);
3.4.10. 2-(2,4-Dimethylphenyl)-1-morpholino-2-(piperidin-1-yl)
ethanone (5j). Pale yellow oil. IR (film) 3030, 2916, 2844,1626,1418,
13C NMR (100 MHz, CDCl3)
d
171.6, 137.5, 135.5, 130.7, 127.3, 127.2,
1256, 1224, 1165, 1104, 1030, 994, 848 cmꢀ1 1H NMR (400 MHz,
;
125.9, 71.7, 52.7, 50.4, 28.6, 26.4, 24.4, 20.5; HRMS-ESI (m/z):
CDCl3)
d
7.22 (1H, d, J¼8.0 Hz, ArH), 7.02e6.96 (2H, m, ArH), 4.49 (1H,
[MþH]þ calcd for C18H29N2O: 289.2274. Found: 289.2271.
s, CHCO), 3.82e3.14 (8H, m, morpholinyl-CH2), 2.75e2.65 (2H, m,
piperidinyl-NCH2), 2.60e2.49 (2H, m, piperidinyl-NCH2), 2.39 (3H, s,
3.4.5. N,N-Dimethyl-2-(2-methylphenyl)-2-(piperidin-1-yl)acet-
amide (5e). Pale yellow oil. IR (film) 3020, 2930, 2850, 2752, 1645,
1487, 1454, 1396, 1335, 1306, 1260, 1217, 1136, 1117, 1103, 1055, 1036,
ArCH3), 2.30 (3H, s, ArCH3), 1.59e1.39 (6H, m, piperidinyl-CH2); 13
C
NMR (100 MHz, CDCl3) d 170.5,137.2, 137.0, 131.6, 131.3, 128.7, 126.4,
67.9, 66.8, 66.2, 51.1, 45.6, 42.0, 26.5, 24.6, 20.9, 19.3; HRMS-ESI
1001, 957, 878, 853, 795, 749 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
(m/z): [MþH]þ calcd for C19H29N2O2: 317.2224. Found: 317.2221.
d
7.38e7.34 (1H, m, ArH), 7.20e7.12 (3H, m, ArH), 4.57 (1H, s, CHCO),
2.93 (3H, s, NCH3), 2.83 (3H, s, NCH3), 2.73e2.65 (2H, m, NCH2),
2.58e2.50 (2H, m, NCH2), 2.45 (3H, s, ArCH3), 1.57e1.39 (6H, m,
3.4.11. 2-(2,3-Dimethylphenyl)-1-morpholino-2-(piperidin-1-yl)
ethanone (5k). Colorless gum. IR (film) 2908, 2844, 1626, 1418,
CH2); 13C NMR (100 MHz, CDCl3)
d
172.0, 137.4, 134.6, 130.5, 128.8,
1255, 1216, 1168, 1106, 1026, 996, 854 cmꢀ1 1H NMR (700 MHz,
;
127.4, 125.7, 67.6, 51.0, 36.7, 35.7, 26.5, 24.7, 19.4; HRMS-ESI (m/z):
CDCl3)
d
7.16 (1H, d, J¼7.7 Hz, ArH), 7.10 (1H, d, J¼7.7 Hz, ArH), 7.06
[MþH]þ calcd for C16H25N2O: 261.1961. Found: 261.1956.
(1H, dd, J¼7.7, 7.7 Hz, ArH), 4.59 (1H, s, CHCO), 3.81e3.30 (6H, m,
morpholinyl-CH2), 3.27e3.08 (2H, m, morpholinyl-CH2), 2.77e2.71
(2H, m, piperidinyl-NCH2), 2.60e2.53 (2H, m, piperidinyl-NCH2),
2.32 (3H, s, ArCH3), 2.30 (3H, s, ArCH3), 1.55e1.41 (6H, m, piper-
3.4.6. N,N-Diethyl-2-(2-methylphenyl)-2-(piperidin-1-yl)acetamide
(5f). Pale yellow oil. IR (film) 2968, 2931, 2850, 1648, 1454, 1427,
1378, 1305, 1250, 1218, 1135, 1118, 1104, 1035, 997, 949, 872, 860,
idinyl-CH2); 13C NMR (175 MHz, CDCl3)
d 170.8, 137.4, 136.0, 134.3,
840, 778, 748 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
7.35 (1H, d,
129.4, 126.6, 125.0, 68.3, 66.8, 66.1, 50.9, 45.6, 41.9, 26.6, 24.7, 20.9,
15.0; HRMS-ESI (m/z): [MþH]þ calcd for C19H29N2O2: 317.2224.
Found: 317.2217.
J¼7.2 Hz, ArH), 7.20e7.11 (3H, m, ArH), 4.53 (1H, s, CHCO), 3.54 (1H,
dq, J¼14.3, 7.0 Hz, CH2CH3), 3.24e3.10 (2H, m, CH2CH3), 2.96 (1H,
dq, J¼14.3, 7.0 Hz, CH2CH3), 2.78e2.69 (2H, m, piperidinyl-NCH2),
2.60e2.51 (2H, m, piperidinyl-NCH2), 2.44 (3H, s, ArCH3), 1.57e1.38
(6H, m, piperidinyl-CH2), 1.09 (3H, t, J¼7.0 Hz, CH2CH3), 0.96 (3H, t,
3.4.12. 2-(5-Chloro-2-methylphenyl)-1-morpholino-2-(piperidin-1-
yl)ethanone (5l). Pale yellow gum. IR (film) 2916, 2848, 1624, 1420,
J¼7.0 Hz, CH2CH3); 13C NMR (100 MHz, CDCl3)
d
171.1, 137.5, 134.9,
1395, 1258, 1220, 1104, 1030, 880, 855, 720 cmꢀ1 1H NMR
;
130.5, 128.9, 127.4, 125.6, 67.2, 50.8, 41.0, 40.0, 26.7, 24.7, 19.3, 14.0,
12.7; HRMS-ESI (m/z): [MþH]þ calcd for C18H29N2O: 289.2274.
Found: 289.2270.
(400 MHz, CDCl3)
d
7.40 (1H, d, J¼2.2 Hz, ArH), 7.17 (1H, dd, J¼8.3,
2.2 Hz, ArH), 7.11 (1H, d, J¼8.3 Hz, ArH), 4.51 (1H, s, CHCO),
3.80e3.25 (8H, m, morpholinyl-CH2), 2.73e2.63 (2H, m, piper-
idinyl-NCH2), 2.59e2.48 (2H, m, piperidinyl-NCH2), 2.39 (3H, s,
ArCH3), 1.62e1.40 (6H, m, piperidinyl-CH2); 13C NMR (100 MHz,
3.4.7. N-Methoxy-N-methyl-2-(2-methylphenyl)-2-(piperidin-1-yl)
acetamide (5g). Pale yellow oil. IR (film) 3059, 3018, 2933, 2851,
2749, 1671, 1460, 1411, 1377, 1305, 1287, 1271, 1212, 1172, 1114, 1086,
CDCl3) d 169.5, 136.5, 135.7, 132.1, 131.6, 128.6, 127.7, 68.1, 66.9, 66.3,
51.3, 45.7, 42.2, 26.4, 24.5, 19.0; HRMS-ESI (m/z): [MþH]þ calcd for
1036, 1008, 986, 878, 840, 810, 750 cmꢀ1
;
1H NMR (400 MHz,
C18H26ClN2O2: 337.1677. Found: 337.1671.
CDCl3) d 7.48e7.43 (1H, m, ArH), 7.21e7.12 (3H, m, ArH), 4.75 (1H, s,
CHCO), 3.37 (3H, s, OCH3), 3.13 (3H, s, NCH3), 2.62e2.48 (4H, m,
NCH2), 2.44 (3H, s, ArCH3), 1.60e1.47 (4H, m, CH2), 1.47e1.37 (2H,
3.4.13. 2-(4-Chloro-2-methylphenyl)-1-morpholino-2-(piperidin-1-
yl)ethanone (5m). Pale yellow gum. IR (film) 2920, 2848,1622,1418,
m, CH2); 13C NMR (100 MHz, CDCl3)
d
173.3, 137.6, 134.5, 130.3,
1260, 1210, 1166, 1100, 1028, 996, 844 cmꢀ1 1H NMR (700 MHz,
;
129.0, 127.5, 125.8, 65.9, 60.7, 51.6, 32.2, 26.2, 24.6, 19.5; HRMS-ESI
CDCl3)
d
7.32 (1H, d, J¼8.4 Hz, ArH), 7.18 (1H, d, J¼2.1 Hz, ArH), 7.16
(m/z): [MþH]þ calcd for C16H25N2O2: 277.1911. Found: 277.1908.
(1H, dd, J¼8.4, 2.1 Hz, ArH), 4.50 (1H, s, CHCO), 3.79e3.19 (8H, m,
morpholinyl-CH2), 2.71e2.65 (2H, m, piperidinyl-NCH2), 2.56e2.49
(2H, m, piperidinyl-NCH2), 2.41 (3H, s, ArCH3), 1.59e1.41 (6H, m,
3.4.8. 2-(2-Methylphenyl)-1-morpholino-2-(piperidin-1-yl)ethanone
(5h). Pale yellow gum. IR (film) 3063, 2927, 2852, 2756, 1650, 1486,
1452, 1429, 1360, 1300, 1271, 1228, 1173, 1115, 1068, 1034, 999, 961,
piperidinyl-CH2); 13C NMR (175 MHz, CDCl3)
d 169.8, 139.2, 133.15,
133.13, 130.6, 130.1, 125.7, 67.4, 66.8, 66.2, 51.1, 45.6, 42.0, 26.4, 24.5,
19.3; HRMS-ESI (m/z): [MþH]þ calcd for C18H26ClN2O2: 337.1677.
Found: 337.1670.
910, 856, 789, 749 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 7.37e7.32 (1H,
m, ArH), 7.20e7.14 (3H, m, ArH), 4.54 (1H, s, CHCO), 3.81e3.13 (8H,
m, morpholinyl-CH2), 2.76e2.65 (2H, m, piperidinyl-NCH2),
2.59e2.50 (2H, m, piperidinyl-NCH2), 2.43 (3H, s, ArCH3), 1.59e1.40
3.4.14. 2-(3-Chloro-2-methylphenyl)-1-morpholino-2-(piperidin-1-
yl)ethanone (5n). Colorless oil. IR (film) 2892, 2844, 1624, 1565,
1414, 1294, 1206, 1166, 1104, 1065, 994, 850, 760, 730, 712 cmꢀ1; 1H
(6H, m, piperidinyl-CH2); 13C NMR (100 MHz, CDCl3)
d 170.4, 137.4,
134.5, 130.9, 128.8, 127.7, 125.7, 68.2, 66.9, 66.2, 51.2, 45.7, 42.0, 26.5,
24.7, 19.5; HRMS-ESI (m/z): [MþH]þ calcd for C18H27N2O2:
303.2067. Found: 303.2060.
NMR (400 MHz, CDCl3)
d
7.33 (1H, dd, J¼8.0, 1.2 Hz, ArH), 7.26 (1H,
dd, J¼8.0, 1.2 Hz, ArH), 7.11 (1H, dd, J¼8.0, 8.0 Hz, ArH), 4.60 (1H, s,
CHCO), 3.82e3.12 (8H, m, morpholinyl-CH2), 2.80e2.69 (2H, m,
piperidinyl-NCH2), 2.61e2.51 (2H, m, piperidinyl-NCH2), 2.48 (3H,
s, ArCH3), 1.58e1.40 (6H, m, piperidinyl-CH2); 13C NMR (100 MHz,
3.4.9. 2-(2,5-Dimethylphenyl)-1-morpholino-2-(piperidin-1-yl)etha-
none (5i). Pale yellow gum. IR (film) 2912, 2836, 1612, 1412, 1292,
1260, 1206, 1160, 1104, 1065, 1026, 990, 908, 846, 808, 786 cmꢀ1; 1H
CDCl3)
d 170.0, 136.6, 135.6, 135.5, 128.8, 127.4, 126.3, 68.2, 66.8,