S. Royo et al. / Tetrahedron: Asymmetry 17 (2006) 2393–2400
2399
yield). Mp 235 ꢁC (diisopropyl ether). IR (Nujol) m 3409,
3200–2850, 1725, 1705 cmꢀ1 1H NMR (CDCl3,
94% yield). Mp 167 ꢁC. [a]D = +53.9 (c 0.60, MeOH)
[lit.15 +49.7 (c 0.50, MeOH)]. Spectroscopic data are iden-
tical to those reported for rac-10.
.
300 MHz) d 1.15 (s, 9H), 4.28 (m, 1H), 4.56 (m, 1H),
5.16 (m, 1H), 7.12–7.78 (m, 8H). 13C NMR (CDCl3,
75 MHz) d 28.05, 48.77, 55.13, 80.47, 119.85, 120.30,
124.65, 124.98, 127.42, 127.95, 128.40, 128.92, 140.78,
141.20, 142.38, 142.80, 155.80, 175.36. HRMS (ESI)
C20H21NO4Na [M+Na]+: calcd 362.13628, found
362.13558.
4.19. Synthesis of (R)-2-(N-tert-butoxycarbonylamino)-2-(9-
fluorenyl)acetic acid, (R)-10
An identical procedure to that described above was applied
to transform (R)-12 (1.270 g, 2.96 mmol) into (R)-10
(999 mg, 2.95 mmol, 100% yield). Mp 167 ꢁC. [a]D =
ꢀ53.8 (c 0.62, MeOH). Spectroscopic data are the same
as those described for rac-10.
4.16. Synthesis of benzyl 2-(N-tert-butoxycarbonylamino)-2-
(9-fluorenyl)acetate, rac-12
A
freshly prepared solution of phenyldiazomethane
(12.83 mmol) in benzene (90 mL) was added slowly to a
suspension of rac-10 (2.90 g, 8.55 mmol) in benzene
(25 mL) at room temperature until a permanently coloured
solution was obtained. Excess diazoalkane was then de-
stroyed by the addition of a small quantity of silica gel.
The crude product obtained after evaporation of the sol-
vent was purified by column chromatography (eluent: hex-
anes/ethyl acetate 8/2) to afford pure rac-12 as a white solid
(3.23 g, 7.53 mmol, 88% yield). Mp 104 ꢁC (hexanes/ethyl
Acknowledgements
´
Financial support from Ministerio de Educacion y Ciencia
(project CTQ2004-5358) and Gobierno de Aragon (re-
´
search group E40, predoctoral fellowship for S.R.) is grate-
fully acknowledged. This project has been funded in whole
or in part with Federal funds from the National Cancer
Institute, National Institutes of Health, under Contract
Number N01-CO-12400.
1
acetate). IR (Nujol) m 3441, 1736, 1712 cmꢀ1. H NMR
(CDCl3, 300 MHz, 60 ꢁC) d 1.28 (s, 9H), 4.54 (m, 2H),
5.13 (s, 2H), 5.18 (m, 1H), 7.12–7.38 (m, 10H), 7.55–7.70
(m, 3H). 13C NMR (CDCl3, 75 MHz) d 28.07, 49.24,
55.29, 67.36, 79.88, 119.71, 120.07, 124.71, 124.74,
127.12, 127.21, 127.74, 127.98, 128.43, 128.53, 134.96,
141.14, 141.26, 142.10, 142.83, 155.34, 171.16. HRMS
(ESI) C27H27NO4Na [M+Na]+: calcd 452.18323, found
452.18326.
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Caution: Phenyldiazomethane must be handled with care in
a well-ventilated hood.
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4.18. Synthesis of (S)-2-(N-tert-butoxycarbonylamino)-2-(9-
fluorenyl)acetic acid, (S)-10
A solution of (S)-12 (1.086 g, 2.53 mmol) in ethyl acetate
(50 mL) was hydrogenated at room temperature in the
presence of 10% palladium–carbon (110 mg). After 8 h, fil-
tration of the catalyst and evaporation of the solvent
afforded pure (S)-10 as a white solid (803 mg, 2.37 mmol,