2240
J. Oxelbark, S. Claeson / Tetrahedron: Asymmetry 13 (2002) 2235–2240
which resulted in vigorous gas evolution. The organic
solvent was evaporated in vacuo. The resulting aqueous
solution was made alkaline with aqueous NaOH, and
the solution was extracted with CHCl3. The amine was
precipitated from the dried and filtered solution with
HCl (g), and after filtration liberated by treatment with
aq. NaOH and CHCl3. Drying over MgSO4, filtration
and evaporation in vacuo yielded the amine (0.69 g,
38% yield based on the acid). 1H NMR (400 MHz,
CDCl3) l: 8.31 (d, 1H, J=9.6 Hz) 8.20–7.98 (m, 7H),
7.89 (d, 1H, J=8 Hz), 3.41 (t, 2H, J=7.8 Hz), 2.89 (t,
2H, J=7 Hz), 2.03 (p, 2H, J=7.4 Hz); GC–MS: M+
1=260.
dropwise at −21°C, and the solution stirred at 0°C for
a further 6 h. The solvent was evaporated and the
residue taken up in ethyl acetate (50 ml). The solution
was washed with dilute HCl (3×5 ml), saturated sodium
bicarbonate (3×5 ml), brine (3×5 ml) and dried
(MgSO4). Evaporation and trituration of the residue
with diethyl ether yielded 2 (0.215 g, 48%). The product
was purified further by flash chromatography, eluting
with 5% isopropanol in chloroform. 1H NMR (400
MHz, CDCl3) l: 8.20–7.96 (m, 8H) 7.74 (d, 1H, J=8
Hz), 7.69 (s, 2H, o-PhH), 7.61 (s, 2H, o-PhH), 7.23 (s,
1H, p-PhH), 6.95 (s, 1H, p-PhH), 6.40 (br t, 1H, NH),
6.28 (br t, 1H, NH), 6.04–6.10 (m, 2H, CH), 3.56–3.10
(m, 6H), 2.34 (s, 6H, ArCH3), 2.14 (s, 6H, ArCH3),
1.90–2.02 (m, 2H), 1.50–1.38 (m, 2H), 0.81 (t, 2H,
J=7.6 Hz). Elemental analysis: Found: C, 75.6; H, 6.6;
N, 4.0; O, 13.5, expected: C, 75.8; H, 6.3; N, 4.0; O,
13.8%.
4.6. (R,R)-O,O%-Bis(dimethylbenzoyl)tartaric anhydride,
7
A slurry of 3,5-dimethylbenzoic acid (8.65 g) in SOCl2
(13.7 g, 2 equiv.) was heated with stirring at 60°C until
no more gas evolved and a clear solution resulted (2 h).
Evaporation under reduced pressure gave a clear oil to
which tartaric acid (2.88 g, 0.3 equiv.) was added. The
flask was fitted with an air cooler and a drying tube,
and the mixture was heated from 80 to 140°C over 3 h
with stirring, until the tartaric acid was dissolved. Ben-
zene (85 ml dried over CaCl2) was added, and the
solution was left to crystallize. The precipitate was
collected and dried in vacuo (4.49 g, 60%). Occasionally
3,5-dimethylbenzoic acid was found in the precipitate.
A further recrystallization from dry benzene provided
[h]589=−69 (c 0.26 dioxane). Mp: 232–234°C.
Acknowledgements
This work was supported by grants from AstraZeneca
R&D Mo¨lndal, Eka Chemicals AB and Selchem.
1
References
the pure anhydride in that case. H NMR (400 MHz,
CDCl3) l: 7.70 (s, 4H) 7.29 (s, 2H), 5.96 (s, 2H), 2.38
(s, 12H).
2. Wilkins, S. M.; Taylor, D. R.; Smith, R. J. J. Chro-
matogr. A 1995, 697, 587–590.
4.7. (R,R)-N-Propyl-O,O%-bis(dimethylbenzoyl)tartaric
acid monoamide, 8
3. Monser, L. I.; Greenway, G. M.; Ewing, D. F. Tetra-
hedron: Asymmetry 1996, 7, 1189–1198.
4. Dutton, J. K.; Knox, J. H.; Radisson, X.; Ritchie, H. J.;
Ramage, R. J. Chem. Soc., Perkin Trans. 1 1995, 2581–
2587.
5. Monser, L. I.; Greenway, G. M. Analyst 1997, 122,
719–726.
6. Kelly, E. J.; Haddleton, D. M.; Crout, D. H. G.; Ross,
P.; Dutton, J. Chem. Commun. 1999, 1233–1234.
7. Liu, Y.; Svec, F.; Fre´chet, J. M. J. Anal. Chem. 1997, 69,
61–65.
8. Xu, M.; Brahmachary, E.; Janco, M.; Ling, F. H.; Svec,
F.; Fre´chet, J. M. J. J. Chromatogr. A 2001, 928, 25–40.
9. Nakano, T. J. Chromatogr. A 2001, 906, 205–225.
10. Sandberg, A.; Markides, K.; Heldin, E. J. Chromatogr. A
1998, 828, 129–156.
Propylamine (1.43 ml, 2.2 equiv.) was added dropwise
to a stirred suspension of 7 (3.12 g) in CH2Cl2 (12 ml)
at 0°C. The resulting white slurry was left at rt for 1 h,
and evaporated in vacuo. The residue was taken up in
ethyl acetate (100 ml) and washed with dilute HCl
(2×10 ml), and brine (2×10 ml). After drying, filtration
and evaporation of the organic phase, the residue was
recrystallized from 2-propanol/hexane (1/1). Grinding
and drying of the crystals (60°C at high vacuum for 24
1
h) provided the acid free of 2-propanol (3.7 g, 90%). H
NMR (400 MHz, CDCl3) l: 7.66 (s, 2H) 7.64 (s, 2H),
7.24 (s, 1H), 7.20 (s, 1H), 6.32 (br t, 1H, J=5.8 Hz,
NH), 6.04 (d, 1H, J=4 Hz, CH), 5.99 (d, 1H, J=4 Hz,
CH), 3.26–3.38 (m, 1H, J=6.8 Hz, NCH2), 3.14–3.24
(m, 1H, J=6.8 Hz, NCH2), 2.35 (s, 6H, ArCH3), 2.33
(s, 6H, ArCH3), 1.48 (p, 2H, J=7.3 Hz, CH2), 0.85 (t,
3H, J=7.4 Hz, CH3). Mp: 160°C (decomposes).
11. Grieb, S.; Matlin, S.; Belunger, A.; Ross, P. J. High Res.
Chromatogr. 1995, 18, 761–763.
12. Wan, Q. H.; Shaw, P. N.; Davies, M. C.; Barrett, D. A.
J. Chromatogr. A 1997, 765, 187–200.
13. Wan, Q. H.; Shaw, P. N.; Davies, M. C.; Barrett, D. A.
4.8. (R,R)-N-Propyl-N%-3(1-pyrenyl)propyl-O,O%-bis-
(dimethylbenzoyl)tartaramide, 2
J. Chromatogr. A 1997, 786, 249–257.
14. Salvador, A.; Herbreteau, B.; Dreux, M.; Karlsson, A.;
Gyllenhaal, O. J. Chromatogr. A 2001, 929, 101–112.
15. Nowakowski, R.; Bielejewska, A.; Duszczyk, K.; Sybil-
ska, D. J. Chromatogr. A 1997, 782, 1–11.
16. Allenmark, S. G.; Andersson, S.; Mo¨ller, P.; Sanchez, D.
Chirality 1995, 7, 248–256.
N-Methylmorpholine (68 ml, 1 equiv.) and ethylchloro-
formate (59 ml, 1 equiv.) was added dropwise to a
stirred solution of 8 (282 mg) in dry THF (8 ml) at
−21°C. After 20 min, a solution of pyrenpropylamine 6
(0.164 g, 1 equiv.) in dry THF (2 ml) was added