3.6 mmol) as described above (580 mg, 59%); [a]3D3 −47.87 (c 1,
CHCl3); m/z [EI] 272 ([M]+); mmax (film)/cm−1 1742 (ester) and
1703 (urethane); dH (250 MHz, C2HCl3) 1.45 [18H, 2s, C(CH3)3],
1.85 (2H, m, H-4), 2.19 (1H, m, H-3S), 3.45 (2H, m, H-5) and
4.15 (1H, 2d, H-2); dC (125.8 MHz, C2HCl3) 23.37 and 24.16 (C-
4), 27.96 and 28.32 [C(CH3)3], 28.38 and 29.84 [C(CH3)3], 30.72
(m, C-3), 46.26 and 46.47 (C-5), 59.66 (C-2), 79.38 and 79.58
[OC(CH3)3], 80.78 [OC(CH3)3], 153.95 and 154.28 (urethane) and
172.29 (ester).
1.96 (2H, m, H-4), 2.29 (1H, m, H-3S), 3.25 (1H, m, H-5A), 3.38
(1H, m, H-5B) and 4.0 (1H, d, J2,3S 8.48, H-2); dC (125.8 MHz,
C2HCl3) 25.53 (C-4), 30.8 (m, C-3), 47.52 (C-5), 63.10 (C-2) and
174.47 (acid).
(2S)-[3,3-2H2]-Proline (1d)
This was prepared from tert-butyl (2S)-[3,3-2H2]-N-tert-
butoxycarbonylprolinate 18c (960 mg, 3.51 mmol) as described
above and the product was purified by dissolving in methanol and
boiling with decolourising charcoal (240 mg, 53%); mp 227 ◦C
(decomp.); [a]3D3 −63.53 (c 1, MeOH) m/z [+ve FAB (thioglycerol)]
118 ([M + H]+); mmax (film)/cm−1 1624 (acid); dH (360 MHz,
C2H3O2H) 1.96 (2H, m, H-4), 3.25 (1H, m, H-5A), 3.38 (1H, m,
H-5B) and 4.0 (1H, s, H-2); dC (125.8 MHz, C2HCl3) 25.45 (C-4),
30.6 (m, C-3), 47.54 (C-5), 63.05 (C-2) and 174.55 (acid).
tert-Butyl (2S)-[3,3-2H2]-N-tert-butoxycarbonylprolinate (18c)
This was prepared from tert-butyl (2S,4S)-[3,3-2H2]-N-tert-
butoxycarbonyl-4-O-para-toluenesulfonyloxyprolinate 17c (1.75 g,
3.95 mmol) as described above (960 mg, 89%), m/z [EI] 273 [(M)+];
mmax (film)/cm−1 1740 (ester) and 1702 (urethane); dH (250 MHz,
C2HCl3) 1.45 [18H, 2s, C(CH3)3], 1.85 (2H, m, H-4), 3.45 (2H, m,
H-5) and 4.15 (1H, 2s, H-2).
Acknowledgements
We thank the EPSRC for studentships (to P. D. and C. A. S.)
(2S)-Proline (1)
tert-Butyl (2S)-N-tert-butoxycarbonylprolinate 18 (720 mg,
2.66 mmol) was stirred with 6 M aqueous hydrochloric acid (12 ml)
at room temperature for 2 h. The solvent was removed in vacuo and
the residue was dissolved in water (5 ml). The pH was adjusted
from pH 2 to 6 using 2 M aqueous ammonium hydroxide and
the solution was loaded on to a Dowex 50X8 (H+) ion exchange
column. The column was eluted with water until the eluant was
no longer acidic and the product was eluted with 2 M aqueous
ammonium hydroxide. The solvent was removed in vacuo. The
residue was dissolved in water (5 ml) and lyophilised to afford
(2S)-proline 1 as an off-white solid which was recrystallised from
References
1 This work has been published as separate communications, in: (a) P.
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◦
diethyl ether and ethanol (300 mg, 88%); mp 223 C (decomp.);
◦
(lit.15 227–229 C); [a]2D3 −61.48 (c 1.33, MeOH) [lit.15 −83 (c 1,
H2O)]; m/z [ES+] 116 ([M + H]+); mmax (KBr)/cm−1 1624 (acid); dH
(500 MHz, C2H3O2H) 1.96 (2H, m, H-4), 2.1 (1H, m, H-3R), 2.29
(1H, m, H-3S), 3.25 (1H, m, H-5A), 3.38 (1H, m, H-5B) and 4.0
(1H, dd, J2,3R 6.23, J2,3S 8.74, H-2); dC (125.8 MHz, C2HCl3) 25.63
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This was prepared from tert-butyl (2S,3S)-[3-2H1]-N-tert-
butoxycarbonylprolinate 18a (1 g, 3.68 mmol) as described above
and was purified by dissolving in methanol and boiling with
decolourising charcoal (126 mg, 27%), mp 225 ◦C (decomp.);
[a]2D8 −47.2 (c 0.25, MeOH); m/z [ES+] 117 ([M + H]+); mmax
(KBr)/cm−1 1624 (acid); dH (360 MHz, C2H3O2H) 1.96 (2H, m,
H-4), 2.1 (1H, m, H-3R), 3.25 (1H, m, H-5A), 3.38 (1H, m, H-
5B) and 4.0 (1H, d, J2,3R 5.8, H-2); dC (125.8 MHz, C2HCl3) 25.53
(C-4), 30.8 (m, C-3), 48.99 (C-5), 63.09 (C-2) and 174.54 (acid).
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This was prepared from tert-butyl (2S,3R)-[3-2H1]-N-tert-
butoxycarbonylprolinate 18b (580 mg, 2.13 mmol) as described
◦
above (195 mg, 71%); mp 225 C (decomp.); [a]3D2 −57.36 (c 1.1,
MeOH); m/z [+ve FAB (thioglycerol)] 139 ([M + Na]+ and 117
([M + H]+); mmax (film)/cm−1 1626 (acid); dH (360 MHz, C2H3O2H)
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The Royal Society of Chemistry 2006
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