C. Pousset et al. / Tetrahedron: Asymmetry 15 (2004) 3407–3412
3411
4
.8. General procedure for lipase-catalysed hydrolysis
Acknowledgements
A solution of ester (1mmol) in THF (2mL) was added
The authors are grateful to the Boehringer company
(Mannheim) for the generous gift of various lipases.
Moreover, C. Pousset is very grateful to Peptisyntha
S.A. for financial support.
ꢀ
2
to 10 M phosphate buffer (8mL) and water (8mL) at
5ꢂC. The pH was adjusted to 7 with 0.1M HCl and
2
the lipase (250mg) added in one portion. The resulting
suspension was stirred at 150rpm with the pH control-
led by the addition of a 0.1M solution of NaOH using
a pH Stat. When the theoretical quantity of NaOH
was added, the suspension was filtered through a small
pad of Celite to remove the enzyme. The residual ester
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2
(
4
.8.1. (2R±-1-tert-Butoxycarbonyl-2-carbomethoxymeth-
20
ylpyrrolidine. ½aꢁ ¼ þ40:1 (c 12.5, MeOH), ee: 99.1
D
2
5
20
D
{
lit. (S) compound: ½aꢁ ¼ ꢀ38:8 (c 16, MeOH)}.
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olidine. White
.8.2. (2S±-1-tert-Butoxycarbonyl-2-carboxymethylpyrr-
solid:
mp
98–99ꢂC
(hexane);
26
20
½
aꢁ ¼ ꢀ38:6 (c 1.41, DMF) ee: 99.4% {lit. 99–
D
2
D
0
ꢀ1
:
1
3
1
01ꢂC; ½aꢁ ¼ ꢀ39:5 (c 1.9, DMF)} IR (KBr) cm
1
700–2800, 1735, 1655; H NMR (200MHz, CDCl ): d
3
.39 (s, 9H), 1.76 (m, 3H), 2.0 (m, 1H), 2.28 (dd, 1H,
1
997, 38, 677–680.
J = 10.1 and 16.0Hz), 2.80 (m, 1H), 3.30 (m, 2H), 4.10
(
3
. (a) Juaristi, E. In Enantioselective Synthesis of b-Amino
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N. Angew. Chem., Int. Ed. 2003, 42, 5794–5795.
1
3
br s, 1H); C NMR (50MHz, CDCl ): d 23.5, 28.4,
3
3
2
7
1.2, 39.1, 46.3, 53.9, 79.9, 156.0, 177; MS (EI) m/z
29 (1%), 173 (5%), 156 (6%), 128 (13%), 114 (30%),
0 (98%), 57 (100%).
4
. Balaspiri, L.; Penke, B.; Papp, G.; Dombi, G.; Kovacs, K.
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4
.8.3. (2R±-1-tert-Butoxycarbonyl-2-carbomethoxymeth-
20
5. Morley, C.; Knight, D. W.; Share, A. C. J. Chem. Soc.,
Perkin Trans. 1 1994, 6, 2903–2907.
6. (a) Enders, D.; Wiedemann, J. Liebigs Ann. 1997, 699–706;
ylpiperidine. ½aꢁ ¼ þ8 (c = 3,96; CHCl ), ee: 98%
D
3
5
20
D
(
lit. (S) compound ½aꢁ ¼ ꢀ8:3 (c = 2,01; MeOH)).
(
b) OꢀBrien, P.; Porter, D. W.; Smith, N. M. Synlett 2000,
4
.8.4.
(2S±-1-tert-Butoxycarbonyl-2-carboxymethylpi-
1336–1338; (c) Baenziger, M.; Gobbi, L.; Riss, B. P.;
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C. A. P.; Smith, A. D.; Rodriguez-Solla, H. Synlett 2002,
20
peridine. White solid: mp 95ꢂC (hexane), ½aꢁ ¼ ꢀ8
D
5
ꢀ1
(
3
c 1.53, MeOH) ee: 99.3% (lit. 93ꢂC) IR (KBr) cm
1
500–3200, 3011, 2980, 1736, 1639, 1433, 1185;
H
1
146–1148.
NMR (200MHz, CDCl ): d 1.37 (s, 9H), 1.56 (m, 6H),
3
7
8
9
. (a) Nikiforov, T.; Stanchev, S.; Milenkov, B.; Dimitrov, B.
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dron: Asymmetry 2001, 12, 105–110.
2
3
.51 (dd, 2H, J = 3.2 and 8.5Hz), 2.70 (m, 1H),
.90 (dm, 1H), 4.63 (m, 1H); C NMR (50MHz,
1
3
CDCl ): d 18.8, 25.2, 27.4, 28.3, 35.0, 39.1, 47.8,
3
5
1.6, 79.5, 154.7, 171.8; MS (EI) m/z 243 (2%), 187
(
(
5%), 184 (3%), 142 (12%), 128 (42%), 84 (100%), 57
89%).
4
.8.5. (3S±-4-tert-Butoxycarbonyl-3-carbethoxymethyl-
20
morpholine. ½aꢁ ¼ þ35:6 (c 1.15; CH Cl ), ee: 99%.
D
2
2
4
.8.6.
(3R±-4-tert-Butoxycarbonyl-3-carboxymethyl-
morpholine. White solid: mp 82ꢂC (hexane: i-Prop O,
10. (a) Nagai, H.; Shiozawa, T.; Achiwa, K.; Terao, Y. Chem.
Phar. Bull. 1992, 40, 2227–2233; (b) Yamanaka, T.;
Ohkubo, M.; Takahashi, F.; Kato, M. Tetrahedron Lett.
2
20
8
cm
/2), ½aꢁ ¼ ꢀ35:7 (c 1.94, CH Cl ) ee: 99%; IR (KBr)
D
3700–2500, 1713, 1694; H NMR (200MHz,
2
2
ꢀ
1
1
2
004, 45, 2843–2845.
CDCl ): d 1.47 (s, 9H), 2.56 (dd, 1H, J = 6.0 and
3
1
1. (a) Csomos, P.; Kanerva, L. T.; Bernath, G.; F u¨ l o¨ p, F.
Tetrahedron: Asymmetry 1996, 7, 1789–1796; (b) Theil, F.;
Ballschuh, S. Tetrahedron: Asymmetry 1996, 7, 3565–3572;
1
5.4Hz), 2.83 (dd, 1H, J = 8.5 and 15.4Hz), 2.9–3.9
1
3
(
m, 6H), 4.34 (m, 1H); C NMR (50MHz, CDCl ): d
3
2
8.2, 33.4, 39.4, 48.0, 66.7, 68.8, 80.5, 154.5, 175.9; MS
(c) Kaman, J.; Forro, E.; F u¨ l o¨ p, F. Tetrahedron: Asym-
metry 2000, 11, 1593–1600.
(
(
EI) m/z 245 (1%), 190 (2%), 172 (3%), 130 (14%), 114
13%), 100 (5%), 86 (33%), 70 (13%), 57 (100%). Anal.
1
2. (a) Kanerva, L. T.; Csomos, P.; Sundholm, O.; Bernath,
G.; F u¨ l o¨ p, F. Tetrahedron: Asymmetry 1996, 7, 1705–
1716; (b) St u¨ rmer, R.; Ditrich, K.; Siegel, W. US 6063615,
Calcd for C H NO : C, 53.87; H, 7.81; N, 5.71.
19
1
1
5
Found: C, 53.95; H, 7.91; N, 5.59.