The Journal of Organic Chemistry
Note
1-(4-Methoxyphenyl)piperidine (7c).26 Off-white gum (30 mg,
78% yield). Purification: silica chromatography, 0−1.5% (EtOAc + 1%
LCMS (ESI): tR = 1.00 min, [M + H]+ 233.4. HRMS (ESI):
(C14H21N2O) [M + H]+ requires 233.1648, found [M + H]+ 233.1648.
υmax (neat): 2932, 2854, 1635, 1599, 1575, 1485, 1444, 1389, 1267,
1244, 1096, 994, 911, 749 cm−1.
1
Et3N)/cyclohexane. H NMR (400 MHz, CDCl3): δ 1.50−1.58 (m,
2H), 1.67−1.75 (m, 4H), 3.02 (t, J = 5.4 Hz, 4H), 3.76 (s, 3H), 6.82
(d, J = 9.0 Hz, 2H), 6.91 (d, J = 9.0 Hz, 2H). 13C NMR (101 MHz,
CDCl3): δ 24.2, 26.2, 52.3, 55.6, 114.4, 118.7, 147.0, 153.6. LCMS
(ESI): tR = 1.21 min, [M + H]+ 121.3. υmax (neat): 2934, 2802, 1510,
1453, 1243, 1182, 1121, 1041, 920, 823 cm−1.
1-(o-Tolyl)piperidine (7k).31 Off-white gum (14 mg, 40% yield).
Purification: silica chromatography, 0−0.5% (EtOAc + 1% Et3N)/
1
cyclohexane. H NMR (400 MHz, CDCl3): δ 1.54−1.60 (m, 2H),
1.66−1.74 (m, 4H), 2.30 (s, 3H), 2.83 (t, J = 4.9 Hz, 4H), 6.94 (ddd, J
= 7.3, 1.0 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 7.11−7.18 (m, 2H). 13C
NMR (101 MHz, CDCl3): δ 17.8, 24.5, 26.6, 53.4, 119.0, 122.6, 126.4,
130.9, 132.7, 153.0. LCMS (ESI): tR = 1.52 min, [M + H]+ 176.3. υmax
(neat): 2933, 2852, 2801, 1599, 1491, 1451, 1442, 1379, 1326, 1227,
1124, 1106, 1028, 923, 759, 723 cm−1.
Methyl 4-(Piperidin-1-yl)benzoate (7d).27 White solid (32 mg, 73%
yield). Purification: silica chromatography, 0−1.5% (EtOAc + 1%
1
Et3N)/cyclohexane. H NMR (400 MHz, CDCl3): δ 1.59−1.72 (m,
6H), 3.32 (t, J = 4.6 Hz, 4H), 3.85 (s, 3H), 6.84 (d, J = 9.0 Hz, 2H),
7.89 (d, J = 9.0 Hz, 2H). 13C NMR (101 MHz, CDCl3): δ 24.4, 25.4,
48.8, 51.5, 113.6, 118.7, 131.2, 154.5, 167.2. LCMS (ESI): tR = 1.28
min, [M + H]+ 220.3. υmax (neat): 2847, 2843, 1704, 1606, 1516, 1436,
1287, 1247, 1191, 1110, 964, 916, 827, 771, 694 cm−1.
3-(Piperidin-1-yl)pyridine (7l).32 Brown gum (7 mg, 22% yield).
Purification: silica chromatography, 0−75% (EtOAc + 1% Et3N)/
1
cyclohexane. H NMR (400 MHz, CDCl3): δ 1.55−1.65 (m, 2H),
1-(4-Bromophenyl)piperidine (7e).28 White solid (41 mg, 85%
yield). Purification: silica chromatography, 0−1.5% (EtOAc + 1%
1.67−1.76 (m, 4H), 3.19 (t, J = 5.4 Hz, 4H), 7.13 (ddd, J = 8.6, 4.6,
0.7 Hz, 1H), 7.18 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 8.05 (dd, J = 4.5, 1.3
Hz, 1H), 8.31 (d, J = 2.7 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ
24.1, 25.6, 49.9, 122.6, 123.3, 139.0, 140.0, 147.7. LCMS (ESI): tR =
0.94 min, [M + H]+ 163.3. υmax (neat): 2935, 2854, 2810, 1582, 1488,
1451, 1424, 1384, 1346, 1245, 1131, 919, 859, 797, 707 cm−1.
tert-Butyl (3-(Piperidin-1-yl)phenyl)carbamate (7m). White solid
(42 mg, 76% yield). Purification: silica chromatography, 0−5%
1
Et3N)/cyclohexane. H NMR (400 MHz, CDCl3): δ 1.54−1.61 (m,
2H), 1.64−1.73 (m, 4H), 3.12 (t, J = 5.4 Hz, 4H), 6.79 (d, J = 9.0 Hz,
2H), 7.31 (d, J = 9.0 Hz, 2H). 13C NMR (101 MHz, CDCl3): δ 24.2,
25.7, 50.4, 111.1, 118.0, 131.7, 151.2. LCMS (ESI): tR = 1.46 min, [M
+ H]+ 240.2. υmax (neat): 2941, 2858, 2817, 1588, 1494, 1450, 1387,
1340, 1280, 1243, 1223, 1127, 992, 917, 860, 808 cm−1.
1-(4-Chlorophenyl)piperidine (7f).29 White solid (33 mg, 84%
yield). Purification: silica chromatography, 0−1.5% (EtOAc + 1%
Et3N)/cyclohexane. M.p.: 67−69 °C. 1H NMR (400 MHz, CDCl3): δ
1.51−1.61 (m, 2H), 1.65−1.74 (m, 4H), 3.11 (t, J = 5.4 Hz, 4H),
6.82−6.85(m, 2H), 7.15−7.20 (m, 2H). 13C NMR (101 MHz,
CDCl3): δ 24.2, 25.7, 50.6, 117.6, 123.9, 128.8, 150.8. LCMS (ESI): tR
= 1.43 min, [M + H]+ 196.3. υmax (neat): 2940, 2810, 1596, 1492,
1441, 1383, 1338, 1242, 1223, 1127, 993, 916, 858, 808, 747 cm−1.
1-(3-Cyanophenyl)piperidine (7g).30 Off-white gum (24 mg, 64%
yield). Purification: silica chromatography, 0−2.5% (EtOAc + 1%
(EtOAc + 1% Et3N)/cyclohexane. M.p.: 94−95 °C. H NMR (400
1
MHz, CDCl3): δ 1.51 (s, 9 H), 1.53−1.60 (m, 2H), 1.68 (dt, J = 11.2,
5.6 Hz, 4H), 3.14 (t, J = 5.6 Hz, 4H), 6.44 (br. s., 1H), 6.60 (dd, J =
8.2, 2.1 Hz, 1H), 6.68 (dd, J = 7.8, 1.5 Hz, 1H), 7.08 (br. s., 1H),
7.09−7.14 (m, 1H). 13C NMR (101 MHz, CDCl3): δ 24.4, 25.8, 28.4,
50.5, 80.2, 106.6, 109.3, 111.3, 129.3, 139.2, 152.7, 153.0. LCMS
(ESI): tR = 1.36 min, [M + H]+ 277.3. HRMS (ESI): (C16H25N2O2)
[M + H]+ requires 277.1911, found [M + H]+ 277.1914. υmax (neat):
3328, 2933, 1698, 1607, 1532, 1497, 1443, 1366, 1236, 1155, 1053,
1026, 979, 954, 901, 861, 768, 692 cm−1.
1
Et3N)/cyclohexane. H NMR (400 MHz, CDCl3): δ 1.58−1.74 (m,
4-(4-(Piperidin-1-yl)benzyl)morpholine (7n). Colorless oil (38 mg,
6H), 3.19 (t, J = 5.4 Hz, 4H), 7.03 (d, J = 7.3 Hz, 1H), 7.07−7.12 (m,
2H), 7.25−7.31 (m, 1H). 13C NMR (101 MHz, CDCl3): δ 24.1, 25.4,
49.7, 112.9, 118.6, 119.5, 120.1, 121.7, 129.7, 151.9. LCMS (ESI): tR =
1.25 min, [M + H]+ 187.3. υmax (neat): 2937, 2861, 2216, 1595, 1572,
1493, 1438, 1383, 1247, 1123, 996, 955, 784, 688 cm−1.
73% yield). Purification: silica chromatography, 0−45% (EtOAc + 2%
1
Et3N)/cyclohexane. H NMR (400 MHz, CDCl3): δ 1.53−1.61 (m,
2H), 1.66−1.75 (m, 4H), 2.42 (t, J = 4.6 Hz, 4H), 3.14 (t, J = 5.1 Hz,
4H), 3.41 (s, 2H), 3.69 (t, J = 4.9 Hz, 4H), 6.88 (d, J = 8.6 Hz, 2H),
7.17 (d, J = 8.6 Hz, 2H). 13C NMR (101 MHz, CDCl3): δ 24.3, 25.9,
1-(4-(Trifluoromethoxy)phenyl)piperidine (7h). Colorless oil (35
50.7, 53.6, 63.0, 67.1, 116.2, 128.0, 130.0, 151.4. LCMS (ESI): tR =
mg, 71% yield). Purification: silica chromatography, 0−1% (EtOAc +
1.17 min, [M + H]+ 261.4. HRMS (ESI): (C16H25N2O) [M + H]+
requires 261.1961, found [M + H]+ 261.1961. υmax (neat): 2932, 2853,
2804, 1613, 1515, 1453, 1237, 1118, 1006, 915, 866 cm−1.
1
2% Et3N)/cyclohexane. H NMR (400 MHz, CDCl3): δ 1.52−1.62
(m, 2H), 1.65−1.74 (m, 4H), 3.13 (t, J = 5.4 Hz, 4H), 6.88 (d, J = 9.0
Hz, 2H), 7.08 (dd, J = 9.2, 0.9 Hz, 2H). 13C NMR (101 MHz,
CDCl3): δ 24.2, 25.8, 50.7, 116.9, 120.7 (q, JC‑F = 255.3 Hz), 121.8,
141.6 (q, JC‑F = 2.0 Hz), 151.0. 19F NMR (282 MHz, CDCl3): δ
−58.32 (s). LCMS (ESI) tR = 1.48 min, [M + H]+ 246.3. HRMS
(ESI): (C12H15F3NO) [M + H]+ requires 246.1100, found [M + H]+
246.1101. υmax (neat): 2938, 1509, 1260, 1232, 1206, 1155, 1131,
1026, 920, 835, 807 cm−1.
tert-Butyl 5-(Piperidin-1-yl)indoline-1-carboxylate (7o). Off-white
solid (39 mg, 65% yield). Purification: silica chromatography, 0−7%
1
(EtOAc + 1% Et3N)/cyclohexane. M.p.: 88−91 °C. H NMR (400
MHz, CDCl3): δ 1.51−1.56 (m, 2H), 1.55 (s, 9H), 1.66−1.76 (m,
4H), 2.98−3.08 (m, 6H), 3.94 (br. s., 2H), 6.75 (d, J = 8.6 Hz, 1H),
6.80 (s, 1H), 7.35 (d, J = 8.0 Hz, 0.5H), 7.74 (d, J = 8.2 Hz, 0.5H). 13C
NMR (126 MHz, CDCl3): δ 24.2, 26.0, 27.3, 27.8, 28.5, 47.5, 47.7,
52.2, 52.3, 80.0, 81.1, 114.7, 114.8, 114.9, 116.0, 116.4, 131.7, 132.7,
135.3, 136.4, 148.3, 152.5, 152.8. LCMS (ESI): tR = 1.50 min, [M +
H]+ 303.3. HRMS (ESI): (C18H27N2O2) [M + H]+ requires 303.2037,
found [M + H]+ 303.2069. υmax (neat): 2932, 2855, 2793, 1692, 1494,
1453, 1380, 1366, 1331, 1244, 1174, 1140, 1127, 1018, 950, 862, 813,
762 cm−1.
N-Methyl-3-(piperidin-1-yl)benzamide (7i). Off-white solid (27
mg, 62% yield). Purification: silica chromatography, 0−35% (EtOAc +
1% Et3N)/cyclohexane. M.p.: 96−98 °C. 1H NMR (400 MHz,
CDCl3): δ 1.53−1.62 (m, 2H), 1.64−1.73 (m, 4H), 2.98 (d, J = 4.9
Hz, 3H), 3.19 (t, J = 5.1 Hz, 4H), 6.27 (br. s., 1H), 7.02 (ddd, J = 8.3,
2.7, 1.0 Hz, 1H), 7.05−7.10 (m, 1H), 7.24 (t, J = 7.8 Hz, 1H), 7.35−
7.39 (m, 1H). 13C NMR (101 MHz, CDCl3): δ 24.2, 25.7, 26.8, 50.3,
114.9, 116.5, 119.0, 129.0, 135.6, 152.3, 168.8. LCMS (ESI): tR = 0.91
min, [M + H]+ 219.3. HRMS (ESI): (C13H19N2O) [M + H]+ requires
219.1492, found [M + H]+ 219.1492. υmax (neat): 3315, 2934, 2854,
2806, 1636, 1598, 1576, 1543, 1489, 1443, 1365, 1343, 1239, 1127,
940, 755, 693 cm−1.
N,N-Dibutylaniline (7p).33 Brown oil (4 mg, 10% yield).
Purification: silica chromatography, 0−1% (EtOAc + 1% Et3N)/
cyclohexane. 1H NMR (400 MHz, CDCl3) δ 0.95 (t, J = 7.3 Hz, 6H),
1.29−1.40 (m, 4H), 1.52−1.62 (m, 4H), 3.22−3.29 (m, 4H), 6.58−
6.67 (m, 3H), 7.15−7.22 (m, 2H). LCMS (ESI): tR = 1.64 min, [M +
H]+ 206.4. Matches data from: Barker, T. J.; Jarvo, E. R. J. Am. Chem.
Soc. 2009, 131, 15598−15599, DOI: 10.1021/ja907038b.
N,N-Dimethyl-3-(piperidin-1-yl)benzamide (7j). Off-white gum
(38 mg, 82% yield). Purification: silica chromatography, 0−30%
N-Isopropylnaphthalen-2-amine (7q).34 Brown oil (27 mg, 73%
yield). Purification: silica chromatography, 0−1% (EtOAc + 1%
1
(EtOAc + 1% Et3N)/cyclohexane. H NMR (400 MHz, CDCl3): δ
1
1.51−1.63 (m, 2H), 1.65−1.74 (m, 4H), 2.97 (br. s., 3H), 3.09 (br. s.,
3H), 3.17 (t, J = 5.6 Hz, 4H), 6.79 (dd, J = 7.5, 1.1 Hz, 1H), 6.91−6.97
(m, 2H), 7.20−7.25 (m, 1H). 13C NMR (101 MHz, CDCl3): δ 24.3,
25.7, 35.2, 39.5, 50.3, 114.7, 117.2, 117.2, 128.9, 137.2, 152.1, 172.2.
Et3N)/cyclohexane. H NMR (400 MHz, CDCl3): δ 1.26 (d, J = 6.3
Hz, 6H), 3.58 (br. s., 1H), 3.75 (sept, J = 6.3 Hz, 1H), 6.78 (d, J = 2.4
Hz, 1H), 6.82 (dd, J = 8.8, 2.4 Hz, 1H), 7.16 (ddd, J = 8.1, 6.9, 1.1 Hz,
1H), 7.33 (ddd, J = 8.3, 6.9, 1.2 Hz, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.60
F
J. Org. Chem. XXXX, XXX, XXX−XXX