Â
J. Balint et al. / Tetrahedron: Asymmetry 11 (2000) 1323±1329
1327
to 8 by 1 M solution of Na2CO3, then it was extracted with dichloromethane (3Â50 ml), the
organic phase dried over Na2SO4 and evaporated. Yield: 4.3 g of brown oil, to which maleic
acid (2.0 g) was added in isopropanol (7.7 ml) and it was recrystallized twice. Yield: 2.0 g (5.2
ꢀ
mmol, 22.6%), mp 147.5±148.5 C. 1H NMR (CDCl3) 1.22 (m, 3H, H2Me), 1.28 (m, 1H, H4 ), 1.80
00
0
0
00
0
00
00
(m, 5H, H4 , 2ÂH2 , 2ÂH3 b), 2.30 (s, 3H, H4 Me), 2.55 (m, 1H, H2 b), 2.77 (m, 1H, H2 ), 3.01
00
(m, 1H, H3), 3.31 (m, 1H, H2 b), 3.61 (m, 1H, H2 ), 3.80 (m, 1H, H3), 4.29 (m, 1H, H2), 6.26
00
0
0
0
(s, 2H, maleic acid), 7.21 (d, 1H, H5 , 7.77 Hz), 7.45 (d, 1H, H6 , 7.69 Hz), 7.57 (s, 1H, H2 ).
FT-IR (KBr, cm^1): 3405, 3050, 2940, 1863, 2780, 1673, 1582, 1458, 1353, 1280, 1245, 1202, 1174,
1112, 1013, 864, 728; calcd for C20H27NO6: C 63.65, H 7.21, N 3.71; found: C 63.60, H 7.24, N
3.72.
3.5.1. Preparation of the free bases
M1-Maleate (5.0 g, 13.25 mmol) was dissolved in a solution of NaOH (1.3 g, 32.5 mmol) in
water (15 ml). The mixture was extracted with ethyl acetate (3Â5 ml), the organic phase was dried
over Na2SO4 and the solvent was evaporated. Yield: 3.36 g (12.85 mmol, 97%) of oil, which
solidi®ed slowly [mp 62±65ꢀC (recryst. from hexane: 65±67ꢀC)]. H NMR (CDCl3) 1.14 (d, 3H,
1
0
H2Me, 7.13 Hz), 1.38 (m, 2H), 1.52 (m, 4H), 2.27 (s, 3H, H4 Me), 2.43 (m, 5H), 3.02 (m, 1H), 3.74
0
0
(m, 1H), 7.14 (d, 1H, H5, 7.74 Hz), 7.41 (d, 1H, H6 , 7.79 Hz), 7.45 (s, 1H, H2 ). FT-IR (KBr,
cm^1): 3424, 2935, 2852, 2814, 1670, 1608, 1584, 1449, 1423, 1282, 1258, 1174, 1104, 993, 762;
calcd for C16H23NO2: C 73.53, H 8.87, N 5.36; found: C 73.32, H 8.90, N 5.38.
3.6. Resolution of M1
3.6.1. Preparation of S-(+)-M1
To the solution of M1 (3.3 g, 12.63 mmol) in ethyl acetate (10 ml) (S)-camphor-10-sulfonic acid
monohydrate (3.16 g, 12.6 mmol) in 15 ml ethyl acetate was added. The solution was cooled to 0±
5ꢀC, then it was inoculated and the mixture was left to crystallize for 40 min. It was ®ltered,
washed with ethyl acetate (3Â1 ml) and dried: 1.55 g, 3.14 mmol. The precipitate was dissolved in
ethyl acetate (10 ml) and washed with 1 M bicarbonate solution. The organic phase was dried and
evaporated. Yield: 0.81 g (3.1 mmol, [ꢁ]D=+29.0 (c=1, methanol)) of oil.
This procedure was repeated twice. Yield: 1.03 g of white crystals, [ꢁ]D=+50.3 (c=1, meth-
anol), mp 173±174ꢀC, after cleavage 0.52 g (2.0 mmol, 31.5%) of white crystalline base,
[ꢁ]D=+34.1 (c=1, methanol), mp 102±104ꢀC. Its enantiomeric excess was determined with the
1
aid of R-(^)-1-(9-anthryl)-2,2,2-tri¯uoroethanol. In the H NMR spectrum of M1 and the chiral
solvating agent (excess: 2.73) it is recognizable that the signal of H2Me was split into two doublets
(0.92 ppm, 1.07 ppm, Á=76.7 Hz). In the case of the spectrum of (S)-(+)-enantiomer and chiral
solvating agent (excess: 3.13) the peaks at 0.92 ppm were missing, so we could establish that the
optical purity of the sample is higher than 95%.
3.6.2. Preparation of (R)-(^)-M1
The mother liquor of the resolution was washed with 3Â15 ml 1 M solution of Na2CO3. The
organic phase was dried and evaporated: 2.26 g of oil (8.65 mmol, [ꢁ]D=^9.9 (c=1, methanol)).
The (R)-(^)-enantiomer was retrieved like the other, but using (R)-camphor-10-sulfonic acid
monohydrate. Yield: 1.68 g (3.4 mmol) of white crystals, [ꢁ]D=^49.8 (c=1, methanol), mp 170±
172ꢀC, after cleavage 0.81 g (3.10 mmol, 49.1%) of white crystalline base, [ꢁ]D=^33.8 (c=1,
methanol), mp 101±103ꢀC.