H
R. Ramkumar, S. Chandrasekaran
Paper
Synthesis
1H NMR (CDCl3, 400 MHz): δ = 1.16 (s, 9 H, 3 × CH3), 4.95 (s, 2 H, CH2),
7.25–7.27 (m, 2 H, ArH), 7.32 (t, J = 7.6 Hz, 2 H, ArH), 7.38 (t, J = 6.4 Hz,
3 H, ArH), 7.52 (dd, J1 = 7.8 Hz, J2 = 1.2 Hz, 2 H, ArH).
1H NMR (CDCl3, 400 MHz): δ = 1.47 (s, 2 H, CH2), 1.63 (s, 4 H, CH2),
3.28 (s, 2 H, CH2), 3.65 (s, 2 H, CH2), 7.23 (dd, J1 = 8.0 Hz, J2 = 0.8 Hz, 2
H, ArH), 7.49 (dd, J1 = 8.0 Hz, J2 = 0.8 Hz, 2 H, ArH).
13C NMR (CDCl3, 100 MHz): δ = 27.39, 48.88, 83.53, 125.51, 127.46,
13C NMR (CDCl3, 100 MHz): δ = 24.46, 25.55, 43.19, 48.72, 123.54,
128.06, 128.45, 129.02, 131.26, 136.40, 137.60, 153.16, 172.07.
128.52, 131.57, 135.25, 169.16
HRMS: m/z calcd for C19H20BrNO3Na [M + Na]+: 412.0524; found:
412.0527.
(4-Bromophenyl)(morpholino)methanone (3g)16
Eluent: PE/EtOAc (85:15); colorless oil; yield: 55.3 mg (91%).
1H NMR (CDCl3, 400 MHz): δ = 3.44–3.71 (m, 8 H, CH2), 7.29 (d, J = 8.0
Hz, 2 H, ArH), 7.55 (d, J = 8.0 Hz, 2 H, ArH).
13C NMR (CDCl3, 100 MHz): δ = 42.60, 48.09, 66.74, 124.14, 128.85,
131.75, 134.09, 169.25.
(2-Iodophenyl)(piperidin-1-yl)methanone (3h)18
Transamidation of Activated Amides; General Procedure
The amide substrate 1, 4, 6, 10, or 11 (1.0 mmol, 1.0 equiv) and the
respective amine 2 (1.3 mmol, 1.3 equiv) in EtOH (1 mL) were taken in
a vial and the reaction mixture was stirred at 45 °C. The reaction was
monitored by TLC. After completion of the reaction, the mixture was
concentrated in vacuo and the residue was purified by column chro-
matography using silica gel (EtOAc/PE) to give the corresponding
transamidation product.
Eluent: PE/EtOAc (85:15); colorless oil; yield: 59.7 mg (93%).
1H NMR (CDCl3, 400 MHz): δ = 1.41–1.71 (m, 6 H, CH2), 3.08–3.21 (m,
2 H, CH2), 3.65–3.79 (m, 2 H, CH2), 7.03 (td, J1 = 7.4 Hz, J2 = 2.0 Hz, 1 H,
ArH), 7.16 (dd, J1 = 7.6 Hz, J2 = 1.6 Hz, 1 H, ArH), 7.35 (td, J1 = 7.6 Hz,
J2 = 0.8 Hz, 1 H, ArH), 7.79 (dd, J1 = 7.6 Hz, J2 = 0.8 Hz, 1 H, ArH).
13C NMR (CDCl3, 100 MHz): δ = 24.45, 25.36, 26.22, 42.46, 47.91,
92.47, 126.78, 128.27, 129.90, 139.13, 142.76, 169.14.
Phenyl(piperidin-1-yl)methanone (3a)8d
Eluent: PE/EtOAc (75:25); colorless oil; yield: 51.3 mg (99%).
1H NMR (CDCl3, 400 MHz): δ = 1.47 (s, 2 H, CH2), 1.63 (s, 4 H, CH2),
3.29 (s, 2 H, CH2), 3.67 (s, 2 H, CH2), 7.35 (d, J = 4.0 Hz, 5 H, ArH).
13C NMR (CDCl3, 100 MHz): δ = 24.51, 25.57, 26.46, 29.62, 43.03,
48.69, 126.70, 128.32, 129.27, 136.43, 170.22.
(2-Iodophenyl)(morpholino)methanone (3i)19
Eluent: PE/EtOAc (85:15); white solid; yield: 59.4 mg (91%); mp 82–
84 °C.
1H NMR (CDCl3, 400 MHz): δ = 3.15 (s, 1 H, CH2), 3.22 (s, 1 H, CH2),
3.55 (s, 1 H, CH2), 3.72–3.79 (m, 5 H, CH2), 7.04 (t, J = 7.6 Hz, 1 H, ArH),
7.16 (d, J = 7.2 Hz, 1 H, ArH), 7.35 (t, J = 7.2 Hz, 1 H, ArH), 7.89 (t, J = 7.6
Hz, 1 H, ArH).
Morpholino(phenyl)methanone (3b)8d
Eluent: PE/EtOAc (85:15); colorless oil; yield: 50.7 mg (97%).
1H NMR (CDCl3, 400 MHz): δ = 2.28–3.59 (m, 8 H, CH2), 7.26 (d, J = 7.6
Hz, 5 H, ArH).
13C NMR (CDCl3, 100 MHz): δ = 42.45, 48.04, 66.66, 126.98, 128.12,
128.41, 129.75, 132.64, 135.12, 170.26.
13C NMR (CDCl3, 100 MHz): δ = 41.95, 47.20, 66.52, 66.63, 92.38,
127.04, 128.45, 130.38, 139.20, 141.62, 169.38.
Phenyl(pyrrolidin-1-yl)methanone (3c)8d
Furan-2-yl(piperidin-1-yl)methanone (3j)20
Eluent: PE/EtOAc (75:25); colorless oil; yield: 47.5 mg (99%).
1H NMR (CDCl3, 400 MHz): δ = 1.68–1.73 (m, 2 H, CH2), 1.76–1.81 (m,
2 H, CH2), 3.26 (t, 2 H, J = 6.4 Hz, CH2), 3.50 (t, J = 6.8 Hz, 2 H, CH2),
7.23–7.25 (m, 3 H, ArH), 7.37–7.39 (m, 2 H, ArH).
13C NMR (CDCl3, 100 MHz): δ = 24.29, 26.22, 46.08, 49.49, 126.95,
128.03, 128.09, 129.67, 130.81, 132.43, 136.95, 169.60.
Eluent: PE/EtOAc (85:15); white solid; yield: 48.9 mg (97%); mp 46–
48 °C.
1H NMR (CDCl3, 400 MHz): δ = 1.48–1.55 (m, 6 H, CH2), 3.55 (s, 4 H,
CH2), 6.31–6.33 (m, 1 H, ArH), 6.79 (dd, J1 = 3.4 Hz , J2 = 0.8 Hz, 1 H,
ArH), 7.34 (d, J = 0.8 Hz, 1 H, ArH).
13C NMR (CDCl3, 100 MHz): δ = 24.51, 25.99, 29.52, 43.88, 47.57,
110.94, 115.38, 143.34, 147.94, 159.10.
Piperidin-1-yl(p-tolyl)methanone (3d)15
Eluent: PE/EtOAc (85:15); colorless oil; yield: 53.4 mg (96%).
(5-Bromofuran-2-yl)(piperidin-1-yl)methanone (3k)21
1H NMR (CDCl3, 400 MHz): δ = 1.44 (s, 2 H, CH2), 1.59 (s, 4 H, CH2),
2.29 (s, 3 H, CH3), 3.29 (s, 2 H, CH2), 3.63 (s, 2 H, CH2), 7.12 (d, J = 6.8
Hz, 2 H, ArH), 7.22 (dd, J1 = 7.4 Hz, J2 = 1.2 Hz, 2 H, ArH).
Eluent: PE/EtOAc (85:15); white solid; yield: 57.1 mg (96%); mp 53–
55 °C.
13C NMR (CDCl3, 100 MHz): δ = 21.29, 24.53, 25.59, 26.43, 43.11,
48.75, 126.83, 128.90, 133.40, 139.33, 170.44.
1H NMR (CDCl3, 400 MHz): δ = 1.61–1.69 (m, 6 H, CH2), 3.65 (s, 4 H,
CH2), 6.37 (d, J = 3.6 Hz, 1 H, ArH), 6.88 (d, J = 3.6 Hz, 1 H, ArH).
13C NMR (CDCl3, 100 MHz): δ = 24.57, 25.71, 29.65, 113.05, 118.03,
123.71, 149.85, 157.91.
(4-Methoxyphenyl)(morpholino)methanone (3e)16
Eluent: PE/EtOAc (85:15); colorless oil; yield: 53.1 mg (95%).
1H NMR (CDCl3, 400 MHz): δ = 3.66 (m, 8 H, CH2), 3.79 (s, 3 H, OCH3),
Piperidin-1-yl(thiophen-2-yl)methanone (3l)20
6.87–6.89 (m, 2 H, ArH), 7.34–7.36 (m, 2 H, ArH).
Eluent: PE/EtOAc (85:15); white solid; yield: 50.9 mg (96%); mp 55–57 °C.
13C NMR (CDCl3, 100 MHz): δ = 55.31, 66.87, 113.72, 127.25, 129.15,
160.83, 170.35.
1H NMR (CDCl3, 400 MHz): δ = 1.59–1.60 (m, 4 H, CH2), 1.65–1.67 (m,
2 H, CH2), 3.61–3.64 (m, 4 H, CH2), 6.99 (td, J1 = 4.0 Hz, J2 = 0.8 Hz, 1 H,
ArH), 7.22 (d, J = 3.2 Hz, 1 H, ArH), 7.38 (d, J = 5.2 Hz, 1 H, ArH).
(4-Bromophenyl)(piperidin-1-yl)methanone (3f)17
13C NMR (CDCl3, 100 MHz): δ = 24.56, 26.08, 26.29, 29.63, 126.49,
128.03, 128.20, 137.56, 163.41.
Eluent: PE/EtOAc (85:15); white solid; yield: 56.5 mg (94%); mp 93–
95 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L