2536
E. Pa´lovics et al. / Tetrahedron: Asymmetry 18 (2007) 2531–2536
measurements were performed by TA Instruments DSC
2920 in the 290–420 K temperature range with 5 K minꢀ1
heating rate. Samples were placed in a hermetically sealed
pan, the measuring cell was purged with 60 ml minꢀ1 nitro-
gen gas.
in water (5 cm3). After 2 days the diastereomeric salt pre-
cipitated. It was filtrated and washed with water
(2 · 0.3 cm3). Then it was treated with concd HCl (2 cm3)
20
in water (5 cm3) to give 0.2 g (R)-(ꢀ)-1, ½aꢁD ¼ ꢀ20:8 (c
2, ethanol).
4.1. Resolution of N-formylphenylalanine by (S)-(+)-2-
benzylaminobutanol (1:1) in water
The mother liquor was acidified with concd HCl (2 cm3)
20
and the precipitate filtrated to give 1.3 g (S)-(+)-1, ½aꢁD
¼
þ4:9 (c 2, ethanol).
A mixture of racemic FPhA (1.93 g, 10.0 mmol) and (S)-
(+)-BAB (1.8 g, 10.9 mmol) was dissolved in water
(5 cm3) under heating. After 12 days, the (S)-(+)-BABÆ
(R)-(ꢀ)-FPhA salt precipitated. This was filtered out and
washed with water (2 · 0.3 cm3), after which it was reacted
with concd HCl (2 cm3) in water (6 cm3). The precipitated
(R)-(ꢀ)-FPhA was filtered off and washed with water
Acknowledgement
The Hungarian OTKA Foundation (Project Nos.: T042725
and F037814) is gratefully acknowledged for financial
support.
(2 · 0.5 cm3). The process yielded 0.64 g of (R)-(ꢀ)-FPhA
20
(66%) ½aꢁD ¼ ꢀ19:3 (c 2, ethanol).
References
The mother liquor of the diastereomeric salt was acidified
with concd HCl (2 cm3), the precipitated (S)-(+)-FPhA
1. Gervais, C.; Grimbergen, R. F. P.; Markovits, I.; Ariaans, G.
J. A.; Kaptein, B.; Bruggink, A.; Broxterman, Q. B. J. Am.
Chem. Soc. 2004, 126, 655.
2. Broxterman, Q. B.; van Echten, E.; Hulshof, L. A.; Kaptein,
B.; Kellogg, R. M.; Minnaard, A. J.; Vries, T. R.; Wynberg,
H. Chim. Oggi—Chem. Today 1998, 16, 34.
3. Kellogg, R. M.; Nieuwenhuijzen, J. W.; Pouwer, K.; Vries, T.
R.; Broxterman, Q. B.; Grimbergen, R. F. P.; Kaptein, B.; La
Crois, R. M.; de Wever, E.; Zwaagstra, K. Synthesis 2003,
1626.
4. Nieuwenhuijzen, J. W.; Grimbergen, R. F. P.; Koopman, C.;
Kellogg, R. M.; Vries, T. R.; Pouwer, K.; van Echten, E.;
Kaptein, B.; Hulshof, L. A.; Broxterman, Q. B. Angew.
Chem., Int. Ed. 2002, 41, 4281.
5. Dalmolen, J.; Tiemersma-Wegman, T. D.; Nieuwenhuijzen, J.
W.; van der Sluis, M.; van Echten, E.; Vries, T. R.; Kaptein,
B.; Broxterman, Q. B.; Kellogg, R. M. Chem. Eur. J. 2005,
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6. Fogassy, E.; Nogradi, M.; Palovics, E.; Schindler, J. Synthesis
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was filtered off and washed with water (2 · 0.5 cm3), the
20
mass of the dried product was 1.0 g. ½aꢁD ¼ þ12:5 (c 2,
ethanol).
4.2. Resolution of N-formylphenylalanine by (S)-(+)-2-
benzylaminobutanol (1:1) in acetone
(a) A mixture of racemic FPhA (19.3 g, 0.1 mol) and
(S)-(+)-BAB (17.9 g, 0.1 mol) was dissolved in hot
acetone (10 cm3). After one night (15 h), the (S)-
(+)-BABÆ(R)-(ꢀ)-FPhA diastereomer salt precipitate
was filtrated and washed with acetone (2 · 1 cm3). It
was reacted with concd HCl (2 · 1 cm3) in water
(5 cm3). The precipitated (R)-(ꢀ)-FPhA was filtered
and washed by water (2 · 0.5 cm3). The process
20
yielded 0.85 g (R)-(ꢀ)-FPhA (88.0%) ½aꢁD ¼ ꢀ62:3
(c 2, ethanol), ee: 83.0%.
The mother liquor of the diastereomeric salt was
evaporated and acidified with concd HCl (3 cm3).
The precipitated (S) -(+)-FPhA was filtered and
7. Overby, L. R.; Ingersoll, A. W. J. Am. Chem. Soc. 1951, 73,
3363.
8. Jacques, J.; Collet, A.; Wilen, S. H. Enantiomers, Racemates,
and Resolutions; Krieger: Malabar, FL, 1981.
washed by water (2 · 0.5 cm3), the mass of the dried
20
product was 0.95 g, (98%), ½aꢁD ¼ þ58:1 (c 2,
´
9. Kozma, D.; Pokol, G.; Acs, M. J. Chem. Soc., Perkin Trans.
ethanol).
2 1992, 435.
´
(b) The work is similar to that described before, but the
diastereomer salt precipitate was filtrated after 3 h.
10. Fogassy, E.; Lopata, A.; Faigl, F.; Darvas, F.; Acs, M.; To}ke,
L. Tetrahedron Lett. 1980, 21, 647.
11. Tamura, R.; Fujimoto, D.; Lepp, Z.; Misaki, K.; Miura, H.;
Takahashi, H.; Ushio, T.; Nakai, T.; Hirotsu, K. J. Am.
Chem. Soc. 2002, 124, 13139.
12. Courvoisier, L.; Mignot, L.; Petit, M. N.; Coquerel, G. Org.
Process Res. Dev. 2003, 7, 1007.
The process yielded 0.90 g (R)-(ꢀ)-FPhA (93.3%)
20
½aꢁD ¼ ꢀ36:8 (c 2, ethanol), ee: 49.1%. The mass of
the dried (S)-(+)-FPhA separated from mother liquor
20
was 0.66 g, (68.5%), ½aꢁD ¼ þ41:8 (c 2, ethanol).
13. Bereczki, L.; Palovics, E.; Bombicz, P.; Pokol, G.; Fogassy,
E. Tetrahedron: Asymmetry 2007, 18, 260.
14. Fogassy, E.; Palovics, E.; Schindler, J. 10th International
Conference of Chemistry, Cluj, 2004; p 342.
4.3. Resolution of N-formylphenylalanine by (S)-(+)-2-benz-
ylaminobutanol and (R)-(+)-1-phenylethylamine (1:0.5:0.5)
in water
15. Marchand, P.; Lefebvre, L.; Querniard, F.; Cardinael, P.;
Perez, G.; Counioux, J. J.; Coquerel, G. Tetrahedron:
Asymmetry 2004, 15, 2455.
Racemic-1 (1.93 g, 10.0 mmol), (S)-(+)-3 (0.67 g,
5.5 mmol) and (R)-(+)-2 (0.9 g, 5.5 mmol) were dissolved