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From Paracetamol to Rolipram
1179
Anal. Calcd for C17H23NO3 (289.37): C, 70.5; H, 8.0; N, 4.8. Found:
C, 69.9; H, 7.8; N, 4.7.
Hz, 1 H), 3.71–3.58 (m, 1 H), 3.38 (dd, J = 9.1, 7.2 Hz, 1 H), 2.71
(dd, J = 16.9, 8.7 Hz, 1 H), 2.46 (dd, J = 16.9, 8.9 Hz, 1 H).
13C NMR (75 MHz, CDCl3) δ = 177.7, 158.8, 134.3, 127.8, 114.4,
55.4, 49.8, 39.8, 38.1.
MS (EI): m/z (%) = 191 (M+, 40), 134 (100).
HRMS (EI): m/z [M]+ calcd for C11H13NO2: 191.0946; found:
Methyl 3-(4-Methoxyphenyl)-4-nitrobutanoate (12a)
Following the procedure for the synthesis of 7, the cinnamate 11a
(850 mg, 4.4 mmol) was converted into 12a (964 mg, 3.8 mmol,
86%); colorless solid; mp 65–68 °C.
IR (KBr): 3443 (w), 1730 (s), 1551 (s), 1252 (m), 833 cm–1 (w).
191.0943.
1H NMR (300 MHz, CDCl3): δ = 7.12 (d, J = 8.6 Hz, 2 H), 6.85 (d,
J = 8.7 Hz, 2 H), 4.67 (dd, J = 12.4, 7.5 Hz, 1 H), 4.57 (dd, J = 12.4,
7.5 Hz, 1 H), 4.02–3.84 (m, 1 H), 3.76 (s, 3 H), 3.61 (s, 3 H), 2.81–
2.60 (2 H).
13C NMR (75 MHz, CDCl3): δ = 171.4, 159.3, 130.3, 128.4, 114.5,
79.7, 55.3, 52.0, 39.6, 37.8.
Anal. Calcd for C11H13NO2 (191.23): C, 69.1; H, 6.8; N, 7.3. Found:
C, 68.8; H, 6.7; N, 7.3.
4-(3-Bromo-4-methoxyphenyl)pyrrolidin-2-one (13b)
Following the procedure for the synthesis of 8 via reduction-cycli-
zation with Zn and aq HCl, 12b (146 mg, 0.4 mmol) was converted
into 13b (58 mg, 0.2 mmol, 49%); colorless solid; mp 153–155 °C.
MS (ESI): m/z (%) = 207 (80), 147 (100).
HRMS (ESI): m/z [M + Na]+ calcd for C12H15NO5 + Na: 276.0848;
found: 276.0868.
IR (KBr): 3196 (m), 1687 (s), 1497 (m), 1256 (s), 1054 cm–1 (m).
1H NMR (300 MHz, CDCl3): δ = 7.43 (d, J = 2.2 Hz, 1 H), 7.15 (dd,
J = 8.5, 2.2 Hz, 1 H), 6.86 (d, J = 8.5 Hz, 1 H), 6.69 (s, 1 H), 3.88
(s, 3 H), 3.75 (dd, J = 9.3, 8.3 Hz, 1 H), 3.68–3.52 (m, 1 H), 3.36
(dd, J = 9.4, 7.1 Hz, 1 H), 2.70 (dd, J = 16.9, 8.8 Hz, 1 H), 2.43 (dd,
J = 16.9, 8.6 Hz, 1 H).
Anal. Calcd for C12H15NO5 (253.10): C, 56.9; H, 6.0; N, 5.5. Found:
C, 57.0; H, 6.0; N, 5.4.
Methyl 3-(3-Bromo-4-methoxyphenyl)-4-nitrobutanoate (12b)
Following the procedure for the synthesis of 7, the cinnamate 11b
(780 mg, 2.9 mmol) was converted into 12b (790 mg, 2.4 mmol,
82%); colorless solid; mp 98–100 °C.
13C NMR (75 MHz, CDCl3): δ = 177.4, 155.2, 135.9, 131.8, 126.8,
112.4, 112.2, 56.4, 49.6, 39.4, 38.0.
MS (EI): m/z (%) = 89 (41), 197 (24), 214 (100), 269 (M+, 46).
IR (KBr): 3167 (w), 1727 (s), 1498 (s), 1284 (m), 1018 (w) cm–1.
HRMS (EI): m/z [M]+ calcd for C11H12BrNO2: 269.0051; found:
1H NMR (300 MHz, CDCl3): δ = 7.38 (d, J = 2.3 Hz, 1 H), 7.12 (dd,
J = 8.5, 2.3 Hz, 1 H), 6.83 (d, J = 8.5 Hz, 1 H), 4.79–4.49 (2 H), 3.90
(m, 1 H), 3.85 (s, 3 H), 3.63 (s, 3 H), 2.74 (dd, J = 16.3, 7.2 Hz, 1
H), 2.68 (dd, J = 16.3, 7.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 171.0, 155.8, 144.2, 132.2, 131.9,
127.8, 112.4, 79.5, 56.4, 52.2, 39.3, 37.7.
269.0062.
Anal. Calcd for C11H12BrNO2 (270.12): C, 48.9; H, 4.5; N, 9.2.
Found: C, 49.0; H, 4.3; N, 5.1.
4-(3-Amino-4-methoxyphenyl)pyrrolidin-2-one (13c)
Following the procedure for the synthesis of 8 via reduction-cycli-
zation with Zn and aq HCl, 12c (100 mg, 0.3 mmol) was converted
into 13c (25 mg, 0.1 mmol, 36%); colorless solid; mp 163–166 °C.
MS (ESI): m/z (%) = 98 (15), 146 (62), 160 (100), 332 (M + H+, 14).
HRMS (ESI): m/z [M + H]+ calcd for C12H15BrNO5: 332.0134;
IR (KBr): 3340 (m), 2938 (w), 1689 (s), 1518 (m), 1230 cm–1 (m).
found: 332.0109.
1H NMR (300 MHz, DMSO-d6): δ = 7.63 (s, 1 H), 6.71 (d, J = 8.2
Hz, 1 H), 6.55 (dd, J = 2.1 Hz, 1 H), 6.43 (dd, J = 8.2, 2.1 Hz, 1 H),
4.66 (s, 2 H), 3.72 (s, 3 H), 3.54 (dd, J = 8.2, 8.2 Hz, 1 H), 3.35–3.47
(m, 1 H), 3.10 (dd, J = 9.4, 7.1 Hz, 1 H), 2.44 (dd, J = 16.4, 8.7 Hz,
1 H), 2.17 (dd, J = 16.3, 8.9 Hz, 1 H).
13C NMR (75 MHz, DMSO-d6): δ = 176.0, 145.2, 137.6, 135.3,
114.3, 112.2, 110.6, 55.3, 48.9, 39.2, 37.9.
Anal. Calcd for C12H14BrNO5 (332.15): C, 43.4; H, 4.2; N, 4.2.
Found: C, 43.2; H, 4.1; N, 4.2.
Methyl 3-(4-Methoxy-3-nitrophenyl)-4-nitrobutanoate (12c)
Following the procedure for the synthesis of 7, the cinnamate 11c
(10.0 g, 42 mmol) was converted into 12c (10.7 g, 36 mmol, 85%);
colorless solid; mp 96–100 °C.
IR (KBr): 2954 (w), 1732 (m), 1529 (s), 1268 (s), 1014 cm–1 (m).
MS (EI): m/z (%) = 106 (23), 134 (98), 149 (89), 206 (100).
HRMS (EI): m/z [M]+ calcd for C11H14N2O2: 206.1055; found:
206.1052.
1H NMR (300 MHz, CDCl3): δ = 7.74 (d, J = 2.4 Hz, 1 H), 7.44 (dd,
J = 8.7, 2.4 Hz, 1 H), 7.06 (d, J = 8.7 Hz, 1 H), 4.75 (dd, J = 12.9,
6.5 Hz, 1 H), 4.63 (dd, J = 12.9, 8.4 Hz, 1 H), 4.05–3.93 (m, 1 H),
3.94 (s, 3 H), 3.64 (s, 3 H), 2.79 (dd, J = 16.5, 7.0 Hz, 1 H), 2.73 (dd,
J = 16.5, 7.7 Hz, 1 H).
Acknowledgment
13C NMR (75 MHz, CDCl3): δ = 170.6, 152.7, 139.7, 133.6, 130.8,
124.5, 114.3, 78.9, 56.7, 52.2, 39.1, 37.3.
MS (EI): m/z (%) = 146 (67), 193 (86), 251 (100), 298 (M+, 3).
We thank Evonik Oxeno for generous donation of solvents and
Umicore (Hanau, Germany) for generous donation of palladium ca-
talysts.
HRMS (EI): m/z [M]+ calcd for C12H14N2O7: 298.0801; found:
298.0794.
Supporting Information for this article is available online at
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Anal. Calcd for C12H14N2O7 (298.25): C, 48.3; H, 4.7; N, 9.4.
Found: C, 48.4; H, 4.6; N, 9.4.
References
4-(4-Methoxyphenyl)pyrrolidin-2-one (13a)
Following the procedure for the synthesis of 8 via reduction-cycli-
zation with Zn and aq HCl, 12a (224 mg, 0.9 mmol) was converted
into 13a (120 mg, 0.6 mmol, 71%); colorless solid; mp 131–132 °C.
IR (KBr): 3203 (m), 2952 (m), 1679 (s), 1541 (s), 1247 cm–1 (s).
1H NMR (300 MHz, CDCl3): δ = 7.17 (d, J = 8.6 Hz, 2 H), 6.88 (d,
J = 8.7 Hz, 2 H), 6.41 (s, 1 H), 3.80 (s, 3 H), 3.75 (dd, J = 9.0, 8.3
(1) Karppanen, H.; Paakkari, P.; Orma, A.-L.; Paakkari, I.
Agents Actions 1979, 9, 84.
(2) Day, J. P.; Lindsay, B.; Riddell, T.; Jiang, Z.; Allcock, R.
W.; Abraham, A.; Sookup, S.; Christian, F.; Bogum, J.;
Martin, E. K.; Rae, R. L.; Anthony, D.; Rosair, G. M.;
Houslay, D. M.; Huston, E.; Baillie, G. S.; Klussmann, E.;
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1174–1180