(R,S)-Baclofen
3745
N-Allylphthalimide (1)
Phthalic anhydride (7 g, 47.28 mmol), allyl amine (3.56 mL, 47.60 mmol),
and triethyl amine (0.7 mL) in toluene (500 mL) were heated under reflux
under a nitrogen atmosphere for 3.5 h with azeotropic removal of water.
The solvent was removed under reduced pressure, diluted with ethyl
acetate, washed with dil. HCl, dried over magnesium sulphate, and concen-
trated to give 1 (8.4 g, 95%); mp: 69–708C (lit. mp: 68–708C);[6] IR (KBr):
1
3022, 2921, 1773, 1703 cm21; H NMR (300 MHz, CDCl3): d 4.27 (d, 2H),
5.15–5.28 (dd, 2H), 5.67–5.89 (m, 1H), 7.70–7.81 (m, 2H), 7.82–7.88
(m, 2H); MS (EI): m/z ¼ 76, 104, 130, 169, 187; 13C NMR (CDCl3): d 40.0,
117.7, 123.3, 131.5, 132.1 134.0, 167.9; anal. calcd. for C11H9NO2 (%): C,
70.58; H, 4.85; N, 7.48. Found: C, 70.46; H, 5.00, N, 7.52.
N-Phthalimido Acetaldehyde (2)
Ozone gas was bubbled through a solution of N-allyl phthalimide (5 g,
26.73 mmol) and CH2Cl2/MeOH (9:1, 200 mL) at 2788C for 30 min until
a blue color persisted. The mixture was purged with N2 until the blue color
disappeared at the same temperature. DMS (35 mL, 1.2 mol) was added,
and the mixture was allowed to warm to room temperature and stirred for
16 h, at which point it was concentrated in vacuo. The residue was crystallized
from DCM/hexane to give the desired compound 2 (3.13 g, 62%). Mp: 110–
1128C (lit. mp: 1118C);[7] IR (KBr): 2931, 1777, 1716, 1613, 1466,
1400 cm21 1H NMR (300 MHz, CDCl3): d 4.56 (s, 2H), 7.71–7.80
;
(m, 2H), 7.82–7.91 (m, 2H), 9.63 (s, 1H, CHO); 13C NMR (CDCl3): d
47.36, 123.67, 131.12, 131.99, 134.35, 167.63, 193.0; MS (EI): m/z ¼ 50,
63, 78, 104, 133, 160 (M-29), 161 (M-28); anal. calcd. for C10H7NO3 (%):
C, 63.49; H, 3.73; N, 7.40. Found: C, 63.54; H, 3.91; N, 7.32.
Ethyl-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)but-2-enote (4)
N-Phthalimido acetaldehyde (2.5 g, 13.23 mmol) (2) and Ph3P55CH-COOEt
(3) (6.9 g, 19.84 mmol) in CH2Cl2 (60 mL) were stirred for 2.5 h at room
temperature. The reaction mixture was washed with water, dried over
MgSO4, and concentrated. The residue was purified on silica gel by eluting
with 1:3 of EtoAc/hexane to give 4 (2.67 g, 78%). Mp: 93–958C (lit. mp:
1
94–968C);[8] IR (KBr): 2923, 2361, 1773, 1714, 1389, 715 cm21; H NMR
(300 MHz, CDCl3): d 1.14 (t, J ¼ 6.1 Hz, 3H), 4.05 (q, J ¼ 6.1 Hz, 2H),
4.34 (d, J ¼ 5.5 Hz, 2H), 5.77 (d, J ¼ 6.1 Hz, 1H), 6.81 (m, 1H), 7.69–7.78
(m, 4H); MS (EI): m/z ¼ 58, 76, 103, 142, 150, 186, 214, 259; 13C NMR
(CDCl3): d 13.9, 37.9, 60.2, 122.8, 123.2, 131.6, 134.0, 140.6, 165.2, 167.2;
anal. calcd. for C14H13NO4 (%): C, 64.86; H, 5.05; N, 5.40. Found: C,
64.69; H, 5.13; N, 5.35.