È
M. Weigl, B. Wunsch / Tetrahedron 58 12002) 1173±1183
1179
calcd C 56.2H 5.90 N 4.10 found C 56.2H 5.93 N 4.03. MS
$CI): m/z $%)344, 342 $MH1, 31, 97), 312, 310 $MH12
CH3OH, 5, 16), 284, 282 $MH12HCO2CH3, 2, 7,), 234
CO2CH3), 3.57 $s, 3H, CO2CH3), 3.59 $s, 3H, CO2CH3),
3.78 $d, J15.8 Hz, 1H, NCH2Ph), 3.85 $d, J15.4 Hz,
1H, NCH2Ph), 4.07mr $s, 2H, NCH2Ph), 4.42 $d, J
17.5 Hz, 1H, COCH2N3), 4.46 $t, J6.0 Hz, 1H, N±CH±
CO2CH3), 4.50 $d, J17.1 Hz, 1H, COCH2N3), 7.19±7.33
$m, 5H, aromat. H). Ratio of rotational isomers 75:25.
mrminor rotamer.
20
$284/2822CH2Cl, 100). [a]589 230.5 $c1.17, CHCl3).
IR $®lm): n $cm21)3031 $w, nCH arom.), 2953 $m, nCH aliph.),
Ä
1740, $s, nCvO, ester), 1662 $s, nCvO, tert. amide), 1437 $m, dCH
aliph.), 1212, 1176 $each m, nCOC), 797 $w, C±Cl), 733, 700
$each m, gmonosubst. aromate). H NMR $400 MHz, d5-nitro-
1
benzene): d2.27±2.62 $m, 4H, CHCH2CH2CO2CH3),
3.57mr $s, 3H, CO2CH3), 3.64 $s, 3H, CO2CH3), 3.67 $s,
3H, CO2CH3), 4.34 $d, J12.8 Hz, 1H, NCH2Ph), 4.40 $d,
J13.2 Hz, 1H, NCH2Ph), 4.53 t, J6.4 Hz, 1H, N±CH±
CO2CH3), 4.58mr $d, J13.2 Hz, 1H, NCH2Ph), 4.68mr $d,
J12.8 Hz, 1H, NCH2Ph), 4.77mr $t, J6.0 Hz, 1H, N±CH±
CO2CH3), 4.78 $d, J16.7 Hz, 1H, COCH2Cl), 4.89 $d,
J17.1 Hz, 1H, COCH2Cl), 7.28±7.54 $m, 5H, aromat.
H). Ratio of rotational isomers 77:23. mrminor rotamer.
1H NMR $400 MHz, d5-nitrobenzene, 1408C): d2.20±
2.28 $m, 1H, CH2CH2CO2CH3), 2.42±2.53 $m, 3H,
CH2CH2CO2CH3), 3.61 $s, 3H, CO2CH3), 3.62 $s, 3H,
CO2CH3), 4.23 $d, J12.8 Hz, 1H, NCH2Ph), 4.29 $d,
J13.2 Hz, 1H, NCH2Ph), 4.66 $t, J6.4 Hz, 1H, N±CH±
CO2CH3), 4.69 $d, J16.2 Hz, 1H, COCH2Cl), 4.79 $d,
J16.7 Hz, 1H, COCH2Cl), 7.24±7.44 $m, 5H, aromat.
H). 13C NMR $100 MHz, d5-nitrobenzene, 1408C): d25.9
$1C, CHCH2CH2CO2CH3), 31.3 $1C, CHCH2CH2CO2CH3),
42.4 $1C, COCH2Cl), 51.2 $1C, NCH2Ph), 51.5 $1C, OCH3),
52.1 $1C, OCH3), 60.2 $1C, N±CH±CO2CH3), 128.3 $3C,
aromat. CH), 129.3 $2C, aromat. CH), 137.6 $1C, aromat.
C), 168.1$1C, CvO), 171.0 $1C, CvO), 173.2 $1C, CvO).
1H NMR $400 MHz, CDCl3): d1.95±2.10 $m, 1H,
CH2CH2CO2CH3), 2.12±2.37 $m, 3H, CH2CH2CO2CH3),
3.42mr $s, 3H, CO2CH3), 3.56 $s, 3H, CO2CH3), 3.57 $s,
3H, CO2CH3), 3.96 $d, J12.8 Hz, 1H, NCH2Ph), 4.02 $d,
J12.4 Hz, 1H, NCH2Ph), 4.20mr $d, J12.8 Hz, 1H,
NCH2Ph), 4.28mr $d, J12.8 Hz, 1H, NCH2Ph), 4.34 $t,
J6.6 Hz, 1H, N±CH±CO2CH3), 4.45mr $d, J15.4 Hz,
1H, CO±CH2±Cl), 4.54 $d, J17.1 Hz, 1H, CO±CH2±
Cl), 4.64 $d, J17.1 Hz, 1H, CO±CH2±Cl), 4.52±4.67mr
$m, 2H, N±CH±CO2CH3, CO±CH2±Cl), 7.23±7.33 $m,
5H, aromat. H). Ratio of rotational isomers 77:23. mr
minor rotamer.
5.1.11. Methyl ꢀS)-3-ꢀ1-benzyl-4-methyl-3,6-dioxopipera-
zin-2-yl)propionate ꢀ14a). A mixture of 12 $5.87 g, 17.2
mmol), a solution of methylamine $8 M in ethanol, 2.6 ml,
20.8 mmol), NEt3 $2.9 ml, 20.9 mmol) and acetonitrile
$80 ml) was stirred for 16 h at room temperature. The
solvent was removed in vacuo and the residue was dissolved
in ethyl acetate $180 ml). The organic layer was washed
with 0.5N HCl $2£120 ml), 0.5N NaOH $150 ml) and a
saturated solution of NaCl $150 ml), dried $Na2SO4), ®ltered
and evaporated in vacuo. The residue was puri®ed by fc
$6 cm, ethyl acetate/acetone8:2, 40 ml, Rf 0.43). Colorless
oil, yield 4.87 g $93.3%). C16H20N2O4 $304.1) HR-MS:
calcd 304.1423 found 304.1427 $11.3 ppm). MS $EI): m/z
$%)304 $M, 37), 272 $M2CH3OH, 11), 213 $M2CH2Ph,
21
10), 181 $2132CH3OH, 28). [a]589 25.5 $c0.55,
CH Cl ). IR $®lm): n $cm21)3052 $w, nCH arom.), 2954
Ä
$w, nCH aliph.), 1732 $m, nCvO, ester), 1658 $s, nCvO, tert. amides),
2
2
1440 $m, d
), 1262, 1175 $each m, nCOC), 733, 701 $each
CH aliph.
m, gmonosubst. aromate). 1H NMR $300 MHz, CDCl3): d
2.0222.30 $m, 2H, CH2CH2CO2CH3), 2.33±2.51 $m, 2H,
CH2CH2CO2CH3), 2.97 $s, 3H, NCH3), 3.69 $s, 3H,
CO2CH3), 3.90 $dd, J8.3, 3.9 Hz, 1H, N±CH±CO), 3.93
$d, J17.1 Hz, 1H, NCH2CO), 4.00 $d, J15.1 Hz, 1H,
NCH2Ph), 4.20 $d, J17.5 Hz, 1H, NCH2CO), 5.30 $d, J
15.1 Hz, 1H, NCH2Ph), 7.25±7.37 $m, 5H, aromat. H).
5.1.12. Methyl ꢀS)-3-ꢀ1-benzyl-4-butyl-3,6-dioxopipera-
zin-2-yl)propionate ꢀ14b). A mixture of 12 $467 mg,
1.37 mmol), butan-1-amine $0.15 ml, 1.52 mmol), NEt3
$0.22 ml, 1.59) and acetonitrile $50 ml) was stirred for
16 h at room temperature. The solvent was evaporated in
vacuo and the residue was dissolved in ethyl acetate
$100 ml). The organic layer was washed with 0.5N HCl
$2£60 ml), 0.5N NaOH $60 ml) and a saturated solution of
NaCl $60 ml), dried $Na2SO4), ®ltered and evaporated in
vacuo. The residue was puri®ed by fc $3 cm, petroleum
ether/ethyl acetate3:7, 10 ml, Rf 0.49). Colorless oil,
yield 443 mg $94%). C19H26N2O4 $346.2) HR-MS: calcd
346.1893 found 346.1889 $21.1 ppm). MS $EI): m/z
$%)346 $M, 36), 314 $M2CH3OH, 6), 259 $M2
CH2CH2CO2CH3, 16), 255 $M2CH2Ph, 13), 223 $2552
5.1.10. Dimethyl ꢀS)-2-[N-ꢀ2-azidoacetyl)-N-benzylamino]-
pentanedioate ꢀ13). A solution of 12 $9.34 g, 27.3 mmol)
and NaN3 $8.89 g, 137 mmol) in acetone $250 ml) was
heated to re¯ux for 8 h. The solvent was removed in
vacuo, the residue was dissolved in Et2O $200 ml), the
Et2O layer was washed with a saturated solution of NaCl
$150 ml) and water $150 ml), dried $Na2SO4) and concen-
trated in vacuo. Colorless oil, yield 9.42 g $99%), petroleum
ether/ethyl acetate 6:4, Rf 0.42. C16H20N4O5 $348.3). MS
$EI): m/z $%)348 $M, 2), 290 $M2CO2CH3, 6), 262
$2902N2, 44), 233 $M22£CO2CH3, 9). MS $CI): m/z $%)
349 $MH1, 100), 321 $MH12N2, 45), 291 $MH12
CO2CH3, 8), 261 $3212CO2CH3, 3), 202 $32122£
21
CH3OH, 39), 195 $2552CO2CH3, 33). [a]589 226.3
$c0.43, CH Cl ). IR $®lm): n $cm21)3030 $w, nCH
Ä
2
2
arom.), 2956 $m, nCH aliph.), 2872 $w, nOCH3), 1736 $s, nCvO,
ester), 1665 $s, nCvO, tert. amides), 1468, 1453 $each m, dCH aliph.),
1259, 1202, 1173 $each m, nCOC), 729, 701 $each m,
1
g
monosubst. aromate). H NMR $300 MHz, CDCl3): d0.91 $t,
J7.3 Hz, 3H, NCH2CH2CH2CH3), 1.20±1.36 $m, 2H,
NCH2CH2CH2CH3), 1.51 $`quint' broad, J7.5 Hz, 2H,
NCH2CH2CH2CH3), 1.96±2.24 $m, 2H, CH2CH2CO2CH3),
2.29±2.48 $m, 2H, CH2CH2CO2CH3), 3.20 $dt, J14.1,
7.3 Hz, 1H, NCH2CH2CH2CH3), 3.47 $dt, J14.1, 7.6 Hz,
1H, NCH2CH2CH2CH3), 3.65 $s, 3H, CO2CH3), 3.84 $dd,
J8.8, 4.0 Hz, 1H, N±CH±CO), 3.90 $d, J17.1 Hz, 1H,
NCH2CO), 4.00 $d, J14.6 Hz, 1H, NCH2Ph), 4.15 $d,
CO CH , 3). IR $®lm): n $cm21)3030 $w, nCH arom.),
Ä
2
3
2954 $w, nCH aliph.), 2109 $s, nN3), 1739 $s, nCvO, ester),
1664 $s, nCvO,
amide), 1436 $m, dCH aliph.), 1217, 1178
tert.
1
$each m, nCOC), 736, 700 $each m, gmonosubst. aromate). H
NMR $400 MHz, CDCl3): d1.93±2.07 $m, 1H,
CH2CH2CO2CH3), 2.13±2.26 $m, 1H, CH2CH2CO2CH3),
2.29±2.38 $m, 2H, CH2CH2CO2CH3), 3.39mr $s, 3H,