10.1002/ejoc.201901649
European Journal of Organic Chemistry
FULL PAPER
CDCl3): δ ppm 7.95 (d, J = 7.46 Hz, 2 H), 7.50–7.61 (m, 1 H), 7.40–7.50
(m, 2 H), 5.95 (q, J = 6.97 Hz, 1 H), 3.31 (br s, 4 H), 1.50 (d, J = 6.97 Hz,
3 H), 1.12 (br s, 6 H). 13C NMR (101 MHz, CDCl3): δ ppm 198.30, 155.20,
135.04, 133.35, 128.76, 128.60, 71.71, 42.09, 41.61, 17.33, 14.06, 13.54.
IR (NaCl): 3563, 3019, 2928, 1693, 1477, 1431, 1381, 1275, 1215, 1175,
1097, 962, 758 cm-1. HRMS (ESI): m/z [M + H]+ calcd for C14H20NO3,
250.1438; found 250.1450.
1.20 (m, 2 H). 19F NMR (377 MHz, CDCl3): δ ppm -123.84 (s, 1 F). 13C
NMR (101 MHz, CDCl3): δ ppm 197.84, 173.08, 173.06, 166.35, 154.59,
153.46 (d, 1JC-F = 246.40 Hz), 148.52, 144.42 (d, 2JC-F = 10.30 Hz), 138.05,
134.59, 133.68, 128.89, 128.55, 123.47 (d, 3JC-F = 7.37 Hz), 113.42 (d, 2JC-
3
=23.63 Hz), 110.14, 105.32 (d, JC-F =2.12 Hz), 72.36, 52.12, 49.97,
F
44.24, 43.74, 34.66, 17.42, 8.25. IR (KBr): 3061, 2988, 2949, 2847, 1719,
1713, 1701, 1697, 1624, 1585, 1493, 1452, 1433, 1342, 1246, 1223, 1138,
1121, 1092, 1026, 995, 968, 924, 893, 837, 802, 704 cm-1. HRMS (ESI):
m/z [M + H]+ calcd for C28H29FN3O6, 522.2035; found 522.2055.
(1-Methyl-2-oxo-2-phenyl-ethyl)
N,N-dibenzylcarbamate
(3k):12a
Obtained as light brown gummy mass; 180.15 mg (48.25%). Purification
1
by flash column chromatography on silica (10% EtOAc/cyclohexane). H
[2-(4-Chlorophenyl)-1-methyl-2-oxo-ethyl] morpholine-4-carboxylate
(5a): Obtained as off white solid; 172 mg (57.77%), mp 60–62 °C.
Purification by flash column chromatography on silica (10%
NMR (400 MHz, CDCl3): δ ppm 8.00 (d, J = 7.63 Hz, 2 H), 7.54–7.65 (m,
1 H), 7.49 (t, J = 7.56 Hz, 2 H), 7.25–7.38 (m, 8 H), 7.19–7.21 (d, J = 8 Hz,
2H), 6.06 (q, J = 6.97 Hz, 1 H), 4.36–4.54 (m, 4 H), 1.56 (d, J = 6.97 Hz, 3
H). 13C NMR (101 MHz, CDCl3): δ ppm 197.95, 156.10, 137.23, 137.17,
134.93, 133.47, 128.86, 128.73, 128.66, 128.11, 128.00, 127.56, 72.75,
49.43, 49.27, 17.35. IR (KBr): 3063, 3028, 2926, 1693, 1597, 1495, 1464,
1452, 1425, 1229, 1134, 1115, 972, 756, 700 cm-1. HRMS (ESI): m/z [M +
H]+ calcd for C24H24NO3 , 374.1751; found 374.1762.
1
EtOAc/cyclohexane) H NMR (400 MHz, CDCl3): δ ppm 7.87–7.92 (m, 2
H), 7.34–7.55 (m, 2 H), 5.88 (q, J = 6.97 Hz, 1 H), 3.58–3.73 (m, 4 H),
3.36–3.56 (m, 4 H), 1.50 (d, J = 6.97 Hz, 3 H). 13C NMR (101 MHz, CDCl3):
δ ppm 196.72, 154.66, 140.13, 133.03, 130.02, 129.25, 72.12, 66.70,
44.64, 44.13, 17.28. IR (KBr): 2967, 2864, 1707, 1693, 1587, 1449, 1425,
1279, 1244, 1111, 972, 850, 764 cm-1. HRMS (ESI): m/z [M + H]+ calcd for
C14H17ClNO4: 298.0841; found 298.0834.
(1-Methyl-2-oxo-2-phenyl-ethyl) N-benzyl-N-methyl-carbamate (3l):12a
Obtained as light yellow gummy mass; 150 mg (50.4%). Purification by
flash column chromatography on silica (10% EtOAc/cyclohexane). 1H
NMR (400 MHz, CDCl3): Mixture of rotational isomers in the ratio 1:1, δ
ppm 7.98 (d, J = 7.70 Hz, 2 H), 7.58 (tt, J = 7.38, 1.24 Hz, 1 H), 7.47 (t, J
= 7.58 Hz, 2 H), 7.18–7.37 (m, 5 H), 5.99 (dq, J = 14.56, 7.05 Hz, 1 H),
4.43–4.60 (m, 2 H), 2.86–2.92 (d, 3 H, -NCH3), 1.54 (br dd, J = 13.88, 7.03
Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ ppm 198.12, 197.98, 156.20,
155.67, 137.27, 134.87, 133.46, 128.82, 128.71, 128.63, 127.76, 127.73,
127.51, 72.49, 72.28, 52.67, 52.61, 34.31, 33.80, 17.39. IR (KBr): 2930,
1697, 1479, 1450, 1402, 1229, 1144, 970, 700 cm-1. HRMS (ESI): m/z [M
+ H]+ calcd for C18H20NO3 , 298.1438; found 298.1432.
[2-(4-Bromophenyl)-1-methyl-2-oxo-ethyl] morpholine-4-carboxylate
(5b): Obtained as light brown solid; 165 mg (48.21%), mp 101–103 °C.
Purification by flash column chromatography on silica (10%
EtOAc/cyclohexane). 1H NMR (400 MHz, CDCl3): δ ppm 7.78–7.83 (m, 2
H), 7.56–7.65 (m, 2 H), 5.86 (q, J = 6.97 Hz, 1 H), 3.58–3.70 (m, 5 H), 3.49
(br d, J = 12.84 Hz, 3 H), 1.49 (d, J = 7.09 Hz, 3 H). 13C NMR (101 MHz,
CDCl3): δ ppm 196.89, 154.60, 133.41, 132.20, 130.07, 128.80, 72.07,
66.66, 44.62, 44.15, 17.23. IR (KBr): 2990, 2957, 2920, 2866, 1697, 1580,
1420, 1277, 1238, 1136, 1113, 1074, 968, 849 cm-1. HRMS (ESI): m/z [M
+ H]+ calcd for C14H17BrNO4 , 342.0335; found 342.0331.
[2-(2-Bromophenyl)-1-methyl-2-oxo-ethyl] morpholine-4-carboxylate
(5c): Obtained as light yellow gummy mass; 202 mg (59.03%). Purification
by flash column chromatography on silica (10% EtOAc/cyclohexane) 1H
NMR (400 MHz, CDCl3): δ ppm 7.58 (br dd, J = 10.70, 1.41 Hz, 1 H), 7.52–
7.63 (m, 1 H), 7.37 (td, J = 7.49, 1.16 Hz, 1 H), 7.27–7.33 (m, 1 H), 5.70
(q, J = 7.09 Hz, 1 H), 3.54–3.77 (m, 4 H), 3.32–3.52 (m, 4 H), 1.47 (d, J =
7.09 Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ ppm 201.38, 154.54, 139.44,
133.65, 131.96, 129.04, 127.39, 119.38, 74.76, 66.65, 44.57, 44.19, 16.27.
IR (KBr):2965, 2920, 2897, 2856, 1701, 1697, 1585, 1460, 1429, 1277,
1242, 1219, 1140, 1115, 1038, 968, 854, 762, 742 cm-1. HRMS (ESI): m/z
[M + H]+ calcd for C14H17BrNO4, 342.0335; found 342.0326.
(1-Methyl-2-oxo-2-phenyl-ethyl)
N-allyl-N-cyclopentyl-carbamate
(3m): Obtained as light yellow oil; 174.64 mg (58%). Purification by flash
column chromatography on silica (10% EtOAc/cyclohexane). 1H NMR (400
MHz, CDCl3): δ ppm 7.93–7.99 (m, 2 H), 7.57 (tt, J = 7.46 Hz, 1 H), 7.43–
7.50 (m, 2 H), 5.96 (d, J = 6.36 Hz, 1 H), 5.84 (br. s., 1 H), 5.07–5.17 (m,
2 H), 4.31 (br. s., 1 H), 3.83 (br. s., 2 H), 1.84 (br. s., 2 H), 1.58–1.72 (m,
3 H), 1.51 (d, J = 6.97 Hz, 6 H). 13C NMR (101 MHz, CDCl3): δ ppm 198.21,
155.57, 135.50, 134.99, 133.39, 128.78, 128.65, 115.70, 72.01, 58.25,
46.34, 29.68, 23.95, 17.32. IR (KBr): 2955, 2870, 1697, 1653, 1449, 1420,
1373, 1256, 1229, 1136, 1101, 970, 772, 700 cm-1. HRMS (ESI): m/z [M +
H]+ calcd for C18H24NO3, 302.1751; found 302.1752.
[2-(2-Iodophenyl)-1-methyl-2-oxo-ethyl]
morpholine-4-carboxylate
(1-Methyl-2-oxo-2-phenyl-ethyl)
N-methoxy-N-methyl-carbamate
(5d): Obtained as light yellow oil; 225.7 mg (57.99%). Purification by flash
column chromatography on silica (10% EtOAc/cyclohexane). 1H NMR (400
MHz, CDCl3): δ ppm 7.92 (dd, J = 8.03, 0.75 Hz, 1 H), 7.59 (dd, J = 7.53,
1.51 Hz, 1 H), 7.41 (td, J = 7.53, 1.00 Hz, 1 H), 7.08–7.20 (td, J = 7.53,
1.00 Hz, 1 H), 5.71 (q, J = 7.03 Hz, 1 H), 3.39–3.67 (m, 8 H), 1.48 (d, J =
7.03 Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ ppm 201.88, 154.56, 142.45,
140.59, 132.13, 128.67, 128.02, 92.11, 74.17, 66.67, 44.60, 44.16, 16.24.
IR (KBr): 2963, 2920, 2897, 2855, 1711, 1693, 1579, 1460, 1427, 1277,
1242, 1219, 1142, 1115, 966, 893, 854, 762, 738, 683 cm-1. HRMS (ESI):
m/z [M + Na]+ calcd for C14H16INNaO4, 412.0016; found 412.0023.
(3n): Obtained as light yellow oil; 78.80 mg (33.21%). Purification by flash
column chromatography on silica (10% EtOAc/cyclohexane). 1H NMR (400
MHz, CDCl3): δ ppm 7.94 (d, J = 7.01 Hz, 2 H), 7.52–7.62 (m, 1 H), 7.46
(t, J = 7.64 Hz, 2 H), 5.96 (q, J = 7.01 Hz, 1 H), 3.72 (s, 3 H), 3.18 (s, 3 H),
1.55 (d, J = 7.09 Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ ppm 197.31,
156.15, 134.60, 133.62, 128.85, 128.59, 72.75, 61.68, 35.52, 17.42. IR
(KBr): 2988, 2974, 2936, 2909, 1719, 1701, 1456, 1420, 1377, 1231, 1165,
1092, 1045, 974, 756, 704 cm-1. HRMS (ESI): m/z [M + Na]+ calcd for
C12H15NNaO4, 260.0893; found 260.0884.
Methyl
1-cyclopropyl-6-fluoro-7-[4-(1-methyl-2-oxo-2-phenyl-
[2-(2,4-Dichlorophenyl)-1-methyl-2-oxo-ethyl]
morpholine-4-
ethoxy)carbonylpiperazin-1-yl]-4-oxo-quinoline-3-carboxylate (3o):
Obtained as off white solid; 230 mg (44.10%), mp 75–77 °C. Purification
by reverse phase flash column chromatography on C-18 column [30%
acetonitrile (0.1% formic acid)/water (0.1% formic acid)]. 1H NMR (400
MHz, CDCl3): δ ppm 8.54 (s, 1 H), 8.04 (d, J = 13.08 Hz, 1 H), 7.96 (d, J
= 7.71 Hz, 2 H), 7.56–7.62 (m, 1 H), 7.48 (t, J = 7.58 Hz, 2 H), 7.24–7.29
(m, 1 H), 5.99 (q, J = 6.97 Hz, 1 H), 3.94 (br s., 1 H), 3.91 (s, 3H), 3.76–
3.85(m, 1H), 3.64–3.75(m, 1H), 3.54–3.63(m, 1H), 3.35–3.48(m, 1H),
3.13–3.34 (m, 4 H), 1.55 (d, J = 7.09 Hz, 3 H), 1.27–1.37 (m, 2 H), 1.10–
carboxylate (5e): Obtained as off white solid; 167 mg (50.27%), mp 80–
82 °C. Purification by flash column chromatography on silica (10%
EtOAc/cyclohexane). 1H NMR (400 MHz, CDCl3): δ ppm 7.58 (d, J = 8.31
Hz, 1 H), 7.45 (d, J = 1.96 Hz, 1 H), 7.32 (dd, J = 8.31, 1.96 Hz, 1 H), 5.69
(q, J = 7.09 Hz, 1 H), 3.59–3.70 (m, 4 H), 3.47 (br s, 4 H), 1.47 (d, J = 7.09
Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ ppm 199.62, 154.53, 137.74,
135.50, 132.47, 130.45, 130.42, 127.36, 74.80, 66.65, 44.60, 44.18, 16.19.
IR (KBr): 2966, 2930, 2868, 2858, 1711, 1697, 1682, 1580, 1553, 1429,
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