792
C.L. Zhang et al. / Chinese Chemical Letters 23 (2012) 789–792
Table 3
Effect of solvent on the yield of N-Cbz product at room temperature.
Entry
Solvent
Time (min)
Yielda (%)
1
2
3
4
5
6
CH2Cl2
THF
10
10
10
10
10
10
57
59
76
57
60
96
EtOH
CH3CN
Et2O
PEG-600
a
Yields of products isolated after column chromatography.
Therefore, we concluded that PEG-600, employed as a promoter and good eco-friendly solvent in our procedure, could
shift the equilibrium toward the right.
In summary, we have achieved an efficient, high-yielding and excellent chemoselective method for protection of
amines by Cbz group at room temperature in PEG-600, an easily recyclable and highly effective reaction medium.
This approach is general and applicable to a wide range of alkyl and aryl amines.
Acknowledgment
We are grateful to the National Science and Technology Project of China (No. 2009ZX09102-054) for financial
support.
References
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[11] Typical experimental procedure: a mixture of amine (1.0 mmol), benzyl chloroformate (Cbz-Cl) (1.2 mmol) and PEG-600 (1.0 mL) was stirred
at room temperature for an appropriate time (see Table 2). After completion of the reaction as monitored by TLC, water was added to the
reaction mixture. The above mixture was extracted with ethyl acetate, and concentrated under reduced pressure to give a crude product which
was further purified by silica gel column chromatography to afford the corresponding N-Cbz derivatives. The PEG-600 was recovered from
aqueous solution by direct distillation of water. Spectral data for selected compounds: entry 3: 1H NMR (300 MHz, CDCl3): d 8.15 (d, 1H,
J = 8.4 Hz), 7.41–7.35 (m, 6H), 7.23 (d, 1H, J = 8.4 Hz), 7.15 (brs, 1H), 5.22 (s, 2H); 13C NMR (100 MHz, CDCl3): d 152.85, 135.58, 133.48,
128.76, 128.71, 128.60, 128.49, 128.25, 127.93, 122.53, 120.63, 67.55; HRMS (ESI-TOF+): m/z [M+H]+ calcd. for C14H12Cl2NO2: 296.0240;
found: 296.0250. Entry 10: 1H NMR (300 MHz, CD3OD): d 7.35–7.24 (m, 5H), 7.15 (d, 2H, J = 8.4 Hz), 6.65 (d, 2H, J = 8.7 Hz), 5.09 (s, 2H);
13C NMR (100 MHz, CD3OD): d 156.37, 154.66, 138.28, 131.95, 129.51, 129.05, 128.92, 122.18, 116.29, 67.42; HRMS (ESI-TOF+): m/z
[M+H]+ calcd. for C14H14NO3: 244.0968; found: 244.0974; IR (KBr) n: 3304, 3060, 2945, 1701, 1538, 1239, 1066, 828 cmÀ1. Entry 19: 1H
NMR (300 MHz, CDCl3): d 7.35 (m, 5H), 5.09 (s, 2H), 3.66–3.50 (m, 3H), 2.01 (m, 4H), 1.37 (m, 2H), 1.22 (m, 2H); 13C NMR (100 MHz,
CDCl3): d 155.62, 136.53, 128.53, 128.13, 69.72, 66.61, 49.31, 33.84, 31.03; HRMS (ESI-TOF+): m/z [M+H]+ calcd. for C14H20NO3:
250.1438; found: 250.1438; IR (KBr) n: 3389, 3341, 2948, 2862, 1687, 1533, 1265, 1229, 1064 cmÀ1
.