896
F. Fernández et al. / Tetrahedron: Asymmetry 20 (2009) 892–896
OH); 2.75 (dd, 1H, J1,2 = 7.3 Hz, J1,5 = 5.7 Hz, H-1); 3.48 (s, 3H,
OCH3); 3.71 (s, 4H, OCH3 + H-2); 4.08–4.24 (m, 3H, H-3 + H-
starting material had been consumed. The reaction mixture was fil-
tered through Celite, eluted with MeOH, and the filtrate was evap-
orated in vacuo to give the amino acid ester 14, which was used in
the next step without further purification.
0
4 + H-5); 4.61 (d, 1H, JH,H = 11.9 Hz, CH2Ph); 4.69 (d, 1H,
0
JH,H = 11.9 Hz, CH2Ph); 4.74 (br, 1H, NH); 5.00 (d, 1H,
0
0
JH,H = 12.1 Hz, CH2Ph); 5.10 (d, 1H, JH,H = 12.1 Hz, CH2Ph); 7.27–
7.35 (m, 10H, H-ar). 13C NMR (CDCl3, ppm): 52.29, 52.60, 55.82,
58.10, 65.23, 72.01, 74.12, 84.00, 84.48, 127.73, 127.76, 128.40,
The crude product (0.06 g, 0.29 mmol) was directly dissolved in
MeOH (5 mL). Saturated aq NaHCO3 (1.5 ml) and CbzCl (0.05 mL,
0.35 mmol) were added and the resulting mixture was stirred at
room temperature. After 4 h TLC (CH2Cl2/MeOH 9:1) showed that
the starting material had been consumed. The reaction mixture
was concentrated to dryness and the residue was partitioned be-
tween EtOAc and H2O. The aqueous layer was extracted with EtOAc
(4 ꢂ 20 mL). The combined organic layers were dried (Na2SO4) and
concentrated in vacuo to provide amino acid derivative 15.
CuSO4 (0.10 g), 2,2-dimethoxypropane (4.6 mL) and PTSA (cata-
lytic amount) were added to a solution of the residue obtained
above (0.10 g, 0.29 mmol) in dry acetone (3 mL). The mixture
was stirred at room temperature under argon for 12 h, after which
TLC (EtOAc/hexane 2:1) showed that the starting material had
been consumed. The reaction mixture was concentrated to dryness
and the residue was dissolved in EtOAc (10 mL) and was washed
with H2O (3 ꢂ 10 mL). The organic layer was dried (Na2SO4) and
concentrated to dryness. The crude product was purified by flash
column chromatography (EtOAc/hexane 1:3) to afford compound
129.64, 130.25, 136.21, 137.31, 154.88, 172.54. IR (NaCl, mmax
,
cmꢀ1): 3377 (br, NH + OH); 1747 (st, C@O); 1665 (st, N–C@O).
MS (CI, m/z, %): 430 (67, [M+H]+); 398 (22, [MꢀOCH3]+); 91 (100,
[CH2Ph]+). Anal. Calcd for C23H27NO7: C, 64.32; H, 6.34; N, 3.26.
Found: C, 64.45; H, 6.19; N, 3.10.
4.8. Methyl (1S,2R,3R,4R,5S)-2-benzyloxy-5-benzyloxycarbonyl-
amino-3-hydroxy-4-methoxycyclopentanecarboxylate 13b
A solution of compound 11b (0.30 g, 0,70 mmol) in dry CH2Cl2
(5 mL) was cooled to ꢀ30 °C. Pyridine (0.2 mL) and Tf2O
(0.17 mL, 1.04 mmol) were added and the mixture was stirred at
ꢀ30 °C for 1 h. TLC (EtOAc/hexane 1:2) revealed that the starting
material had been consumed. The reaction mixture was diluted
with CH2Cl2 (30 mL) and was washed with 10% aq HCl (30 mL)
and brine (30 mL). The organic layer was dried (Na2SO4) and con-
centrated to dryness to give the corresponding triflate 12, which
was used in the next step without further purification.
16 (0.10 g, 0.25 mmol, 80% from 13b) as
a colourless oil.
½
a 1D7
ꢁ
¼ ꢀ74:6 (c 1.2, CHCl3). 1H NMR (CDCl3, ppm): 1.31 (s, 3H,
This crude product (0.39 g, 0.70 mmol) was dissolved in dry
DMF (16 mL) and CF3CO2Na (0.57 g, 4.24 mmol) was added. The
reaction mixture was stirred at 50 °C for 48 h. TLC (EtOAc/hexane
1:2) revealed that the starting material had been consumed. After
the solvent was removed in vacuo, solid residue containing 13a
was directly dissolved in a 1 M solution of MeONa in MeOH
(10 mL) and the solution was stirred for 24 h, when TLC (EtOAc/
hexane 1:2) revealed that the starting material had been con-
sumed. The solvent was removed in vacuo and the residue was di-
luted with CH2Cl2 (20 mL) and was washed with H2O (3 ꢂ 20 mL).
The organic layer was dried (Na2SO4) and concentrated to dryness.
The crude product was purified by flash column chromatography
(EtOAc/hexane 1:2) to afford compound 13b (0.14 g, 0.33 mmol,
CH3); 1.50 (s, 3H, CH3); 3.02–3.04 (m, 1H, H-1); 3.37 (s, 3H, CH3);
3.69 (br, 4H, CH3 + H-4); 4.45–4.50 (m, 2H, H-3 + H-2); 5.08 (d,
0
1H, JH,H = 11.8 Hz, CH2Ph); 5.10 (m, 1H, H-5); 5.15 (d, 1H,
0
JH,H = 11.8 Hz, CH2Ph); 5.35 (br, 1H, NH); 7.30–7.38 (m, 5H, H-
ar). 13C NMR (CDCl3, ppm): 23.7, 26.1, 51.9, 53.2, 57.1, 57.6, 66.2,
79.5, 82.5, 87.3, 111.5, 127.6, 127.7, 128.1, 136.2, 155.1, 170.9. IR
(NaCl, m
max, cmꢀ1): 3327 (br, NH); 1759 (st, C@O); 1659 (st, N–
C@O). MS (CI, m/z, %): 380 (47, [M+H]+); 348 (25, [MꢀOCH3]+);
244 (45 [MꢀCO2Bn]+). Anal. Calcd for C19H25NO7: C, 60.15; H,
6.64; N, 3.69. Found: C, 59.91; H, 6.43; N, 3.87.
Acknowledgement
45% from 11b) as a colourless oil. ½a D22
ꢁ
¼ ꢀ44:9 (c 1.1, CHCl3). 1H
We thank the Spanish Ministry of Science and Innovation for
financial support (CTQ2005-00555 and CTQ2008-03105) and for
F.P.U. grants to Fernando Fernández Nieto and Amalia M.
Estévez.
NMR (CDCl3, ppm): 2.83 (br, 1H, OH); 2.90 (dd, 1H, J1,2 = 7.8 Hz,
J1,5 = 7.3 Hz, H-1); 3.41 (s, 3H, OCH3); 3.50 (dd, 1H, J4,5 = 4.7 Hz,
J4,3 = 2.6 Hz, H-4); 3.72 (s, 3H, OCH3); 4.00 (dd, 1H, J2,1 = 7.8 Hz,
J2,3 = 5.7 Hz, H-2); 4.10 (dd, 1H, J3,2 = 5.7 Hz, J3,4 = 2.6 Hz, H-3);
4.23 (dd, 1H, J5,1 = 7.3 Hz, J5,4 = 4.7 Hz, H-5); 4.57 (d, 1H,
References
0
0
JH,H = 11.4 Hz, CH2Ph); 4.65 (d, 1H, JH,H = 11.4 Hz, CH2Ph); 5.01
0
(d, 1H, JH,H = 12.2 Hz, CH2Ph); 5.04 (d, 1H, JNH,5 = 7.3 Hz, NH);
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0
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4.9. Methyl (1S,2R,3R,4R,5S)-5-benzyloxycarbonylamino-2,3-
isopropylidenedioxy-4-methoxycyclopentanecarboxylate (16)
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