2580
S. Gedey et al. / Tetrahedron: Asymmetry 10 (1999) 2573–2581
cyclodextrin-β 2,3,6-M-9 column (25 m). Before the analysis, the unreacted ethyl ester 1 in the sample
was derivatized with acetic or butyric anhydride in the presence of 4-N,N-dimethylaminopyridine and
pyridine.
1
H NMR spectra were measured on a Bruker 200/Aspect 3000 spectrometer in CDCl (tetramethylsi-
3
lane as internal standard). Mass spectra were recorded on a VG Analytical 7070E instrument equipped
with a Vaxstation 3100 M 76 computer. Elemental analyses were performed with a Perkin–Elmer CHNS-
2
400 Ser II elemental analyzer. Optical rotations were measured with a Jasco DIP-360 polarimeter, and
−1
2
−1
[α] values are given in units of 10 deg cm g .
D
4.2. Gram-scale resolution of ethyl 3-aminobutyrate
Racemic ethyl 3-aminobutyrate (2.33 g, 17.7 mmol) was dissolved in butyl butyrate (178 mmol) and
Chirazyme L2 (5.3 g) was added. The mixture was stirred at room temperature for 2 h. The reaction was
stopped by filtering off the enzyme at 65% conversion. In order to facilitate the separation in the column,
0
the unreacted 1 and product P (R =Bu) were transformed to the corresponding acetamides with acetic
2
anhydride (2 ml, 0.021 mol) in the presence of 4-N,N-dimethylaminopyridine and pyridine (1 ml) by
stirring the reaction mixture overnight. After evaporation, the products were separated on silica gel by
0
elution with petroleum ether:propan-1-ol (100:6), the elution sequence being P (R=Pr, R =Bu) before
3
0
the acetamide of P (R =Bu) and P (R=Pr). After the three products had eluted, the eluent was changed
2
1
to propanol and the acetamide of unreacted (S)-1 was obtained. Evaporation of the solvent gave the
products and the unreacted substrate, except that the amount of P (R=Pr) was too small to be isolated.
1
0
4
.2.1. (R)-P (R=Pr, R =Bu)
1
3
20
1
.32 g, 5.77 mmol; [α]D +16.1 (c=1.0, MeOH); ee 99%. M=229 according to MS. H NMR (200
MHz) δ (ppm): 0.9 (6H, m, 2×CH CH ), 1.2 (3H, d, J=6.6, CHCH ), 1.3 (2H, m, CH CH CH ), 1.6
2
3
3
2
2
2
(
4H, m, CH CH CH , CH CH CH ), 2.1 (2H, t, J=7.4, COCH ), 2.5 (2H, d, J=5.3, CH CO ), 4.0 (2H,
2 2 2 2 2 3 2 2 2
t, J=6.5, CO CH ), 4.3 (1H, m, CH). Analysis: calculated for C H NO : C, 62.85; H, 10.11; N, 6.11;
2
2
12 23
3
found: C, 62.49; H, 10.41; N, 6.11.
0
4
.2.2. Acetamide of (S)-P (R =Bu)
2
0
.46 g, 2.28 mmol; contains 10% of the unreacted substrate 1 and 4% of the produced P . M=201
3
1
according to GLC–MS. H NMR (200 MHz) δ (ppm): 0.9 (3H, t, J=7.25, CH CH ), 1.2 (3H, d, J=6.72,
CHCH ), 1.3–1.7 (4H, m, 2CH ), 1.9 (3H, s, COCH ), 2.5 (2H, d, J=5.16, CH CO ), 4.0 (2H, t, J=6.7,
2
3
3
2
3
2
2
CO CH ), 4.3 (1H, m, CH).
2
2
4
.2.3. Acetamide of (S)-1
20
1
0.83 g, 4.82 mmol; [α]D −22.5 (c=1.0, MeOH); ee 96%. M=173 according to MS. H NMR (200
MHz) δ (ppm) 1.1–1.3 (6H, m, 2CH ), 1.9 (3H, s, COCH ), 2.5 (2H, d, J=5.4, CH CO ), 4.1 (2H, m,
J=7.0, CO CH ), 4.3 (1H, m, CH). Analysis: calculated for C H NO : C, 55.47; H, 8.73; N, 8.09;
3
3
2
2
2
2
8
15
3
found: C, 54.06; H, 8.74; N, 7.54.