914
S. Nag et al.
PAPER
Ethyl 2-[(Benzylamino)methyl]-3-(2-chlorophenyl)-3-hydroxy-
propionate (2b)
White solid; yield: 80%; 4:1 dr; mp 81–84 °C.
IR (KBr): 1725 (CO2Et), 3324 (br, NH and OH) cm–1.
ESI-MS: m/z (%) = 373.1 (100.0) [M+ + 1], 375.1 (36.3) [M+ + 3].
Anal. Calcd for C20H21ClN2O3: C, 64.43; H, 5.68; N, 7.51. Found:
C, 64.54; H, 5.76; N, 7.48.
Ethyl 2-{[Cyano(cyclohexyl)amino]methyl}-3-hydroxy-3-phe-
nylpropionate (3d)
Brown oil; yield: 76%; 2:1 dr.
IR (neat): 1736 (CO2Et), 2208 (CN), 3408 (OH) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.91 (t, J = 7.2 Hz, 3 H, CH3CH2),
1.13–1.36 (m, 15 H, CH3CH2 and 2 × 3 CH2), 1.78–1.82 (m, 8 H,
2 × 2 CH2), 1.82–1.94 (m, 4 H, 2 × CH2), 2.64–2.69 (m, 2 H, 2 ×
CHN), 3.08–3.1 (m, 2 H, CH2), 3.32–3.53 (m, 4 H, CH2 and 2 ×
CH), 4.09–4.16 (m, 4 H, CH2CH3), 4.93 (d, J = 6.0 Hz, 1 H,
CHOH), 5.03 (d, J = 6.0 Hz, 1 H, CHOH), 7.32–7.38 (m, 10 H,
2 × 5 ArH).
1H NMR (200 MHz, CDCl3): d = 0.96 (t, J = 7.2 Hz, 3 H, CH2CH3),
1.31 (t, J = 7.2 Hz, 3 H, CH2CH3), 2.93–3.01 (m, 2 H, CH2), 3.12–
3.15 (m, 2 H, CH2), 3.25–3.31 (m, 2 H, 2 × CH), 3.84–3.98 (m, 6 H,
CH2CH3 and 2 × CH2Ph), 4.18 (q, J = 7.2 Hz, 2 H, CH2CH3), 5.41
(d, J = 2.9 Hz, 1 H, CHOH), 5.70 (d, J = 2.9 Hz, 1 H, CHOH), 7.19–
7.39 (m, 16 H, 2 × 8 ArH), 7.54–7.55 (m, 2 H, 2 × 1 ArH).
ESI-MS: m/z (%) = 348.2 (100.0) [M+ + 1], 350.1 (34.2) [M+ + 3].
Anal. Calcd for C19H22ClNO3: C, 65.61; H, 6.38; N, 4.03. Found: C,
65.66; H, 6.49; N, 3.87.
Ethyl 2-(Anilinomethyl)-3-hydroxy-3-phenylpropionate (14)
Brown oil; yield: 63%; 1:1 dr.
ESI-MS: m/z (%) = 331.2 (100.0) [M+ + 1].
IR (neat): 1722 (CO2Et), 3409 (OH) cm–1.
Anal. Calcd for C19H26N2O3: C, 69.06; H, 7.93; N, 8.48. Found: C,
68.82; H, 8.01; N, 8.44.
1H NMR (300 MHz, CDCl3): d = 1.16–1.36 (m, 6 H, 2 × CH3CH2),
3.12–3.14 (m, 2 H, 2 × CH), 3.31–3.33 (m, 2 H, CH2), 3.39–3.41 (m,
2 H, CH2), 4.16–4.22 (m, 4 H, 2 × CH2CH3), 5.03 (2 merged d,
J = 4.6 Hz, 2 H, 2 × CHOH), 6.52 (d, J = 8.0 Hz, 2 H, 2 × ArH),
6.70–6.75 (m, 2 H, 2 × ArH), 7.14–7.19 (m, 4 H, 2 × 2ArH), 7.31–
7.39 (m, 12 H, 2 × 6 ArH).
Ethyl 2-{[Butyl(cyano)amino]methyl}-3-(2-chlorophenyl)-3-hy-
droxypropionate (3g)
Yellow oil; yield: 70%; 3:2 dr.
IR (neat): 1732 (CO2Et), 2212 (CN), 3437 (OH) cm–1.
1H NMR (200 MHz, CDCl3): d = 0.84–0.97 (m, 6 H, 2 × CH3), 1.11
(t, J = 7.2 Hz, 3 H, CH3CH2), 1.28 (t, J = 7.2 Hz, 3 H, CH3CH2),
1.24–1.62 (m, 8 H, 2 × 2 CH2), 2.83–2.86 (m, 2 H, CH2N), 2.99–
3.03 (m, 2 H, CH2N), 3.26–3.31 (m, 2 H, 2 × CH), 3.45–3.51 (m, 4
H, 2 × CH2N), 4.08 (q, J = 7.2 Hz, 2 H, CH2CH3), 4.24 (q, J = 7.2
Hz, 2 H, CH2CH3), 5.20–5.31 (m, 1 H, CHOH), 5.44–5.47 (m, 1 H,
CHOH), 7.25–7.60 (m, 8 H, 2 × 4 ArH).
ESI-MS: m/z (%) = 300.2 (100.0) [M+ + 1].
Anal. Calcd for C18H21NO3 C, 72.22; H, 7.07; N, 4.68. Found: C,
72.11; H, 7.22; N, 4.87.
Cyanamides 3, 8, 12, and 15 and Ureides 5; General Procedure
NaHCO3 (1.5 equiv) and BrCN (1.2 equiv) were simultaneously
added to a soln of the appropriate secondary amine 2, 7, 11, or 14 (1
equiv) in anhyd benzene (15 mL·g–1 amine) at r.t., and the mixture
was stirred for 15 min (or 12 h for ureides 5). Subsequent evapora-
tion of the benzene under reduced pressure furnished an oily resi-
due, which was extracted with EtOAc (2 × 30 mL) and H2O (50
mL). The organic layers were combined, dried (Na2SO4), and con-
centrated in vacuo; this afforded a crude product, whose purifica-
tion by column chromatography (silica gel, hexane–EtOAc, 90:10
to 85:15) yielded the pure product.
ESI-MS: m/z (%) = 339.1 (100.0) [M+ + 1], 341.1 (34.1) [M+ + 3].
Anal. Calcd for C17H23ClN2O3: C, 60.26; H, 6.84; N, 8.27. Found:
C, 60.11; H, 6.79; N, 8.09.
Ethyl 2-[(1-Benzylureido)methyl]-3-phenylacrylate (5a)
White solid; yield: 72%; mp 150–152 °C.
IR (KBr): 1672 (CONH2), 1694 (CO2Et), 3403 (NH2) cm–1.
1H NMR (200 MHz, CDCl3): d = 1.37 (t, J = 7.2 Hz, 3 H, CH3CH2),
4.20 (s, 2 H, CH2), 4.24–4.35 (m, 4 H, CH2CH3 and CH2Ph), 5.12
(s, 2 H, NH2CO), 6.77–6.80 (m, 2 H, ArH), 7.08–7.11 (m, 3 H,
ArH); 7.22–7.25 (m, 2 H, ArH), 7.33–7.36 (m, 3 H, ArH), 7.89 (s,1
H, =CH).
Ethyl 2-{[Benzyl(cyano)amino]methyl}-3-hydroxy-3-phenyl-
propionate (3a)
Yellow oil; yield: 63%; 3:2 dr.
IR (neat): 1728 (CO2Et), 2214 (CN), 3436 (OH) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.17–1.22 (m, 6 H, 2 × CH3CH2),
3.10–3.21 (m, 4 H, CH2N and 2 × CH), 3.30–3.34 (m, 2 H, CH2N),
4.12–4.20 (m, 8 H, 2 × CH2CH3 and 2 × CH2Ph), 4.82–4.91 (m, 2
H, 2 × CHOH), 7.25–7.39 (m, 18 H, 2 × 9 ArH).
ESI-MS: m/z (%) = 339.1 (100.0) [M+ + 1].
Anal. Calcd for C20H22N3O3: C, 70.99; H, 6.55; N, 8.28. Found: C,
71.10; H, 6.43; N, 8.34.
ESI-MS: m/z (%) = 339.2 (100.0) [M+ + 1].
Ethyl 2-[(1-Benzylureido)methyl]-3-(2-chlorophenyl)acrylate
(5b)
White solid; yield: 77%; mp 145–147 °C.
IR (KBr): 1666 (CONH2), 1705 (CO2Et), 3403 (NH2) cm–1.
Anal. Calcd for C20H22N2O3: C, 70.99; H, 6.55; N, 8.28. Found: C,
71.10; H, 6.73; N, 8.09.
1H NMR (200 MHz, CDCl3): d = 1.39 (t, J = 7.2 Hz, 3 H, CH3CH2),
4.10 (s, 2 H, CH2N), 4.15 (s, 2 H, CH2Ph), 4.32 (q, J = 7.2 Hz, 2 H,
CH2CH3), 5.22 (s, 2 H, NH2), 6.78–6.82 (m, 2 H, ArH), 7.02–7.12
(m, 5 H, ArH), 7.29–7.34 (m, 1 H, ArH), 7.45–7.51 (m, 1 H, ArH),
7.91 (s, 1 H, = CH).
Ethyl 2-{[Benzyl(cyano)amino]methyl}-3-(2-chlorophenyl)-3-
hydroxypropionate (3b)
Yellow oil; yield: 67%; 3:2 dr.
IR (neat): 1730 (CO2Et), 2214 (CN), 3410 (OH) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.28 (t, J = 7.2 Hz, 3 H, CH3CH2),
1.39 (t, J = 7.2 Hz, 3 H, CH3CH2), 3.11–3.20 (m, 1 H, CH), 3.21–
3.35 (m, 3 H, CH and CH2N), 3.48–3.55 (m, 2 H, CH2N), 4.03–4.34
(m, 8 H, 2 × CH2CH3 and 2 × CH2Ph), 5.24 (d, J = 3.6 Hz, 1 H,
CHOH), 5.47 (d, J = 3.6 Hz, 1 H, CHOH), 7.00–7.20 (m, 6 H, 2 × 3
ArH), 7.27–7.37 (m, 10 H, 2 × 5 ArH), 7.40–7.55 (m, 2 H, 2 × 1
ArH).
ESI-MS: m/z (%) = 373.1 (58.1) [M+ + 1], 375.1 (18.8) [M+ + 3].
Anal. Calcd for C20H21ClN2O3: C, 64.43; H, 5.68; N, 7.51. Found:
C, 64.46; H, 5.88; N, 7.37.
Methyl 2-[(1-Benzylureido)methyl]-3-phenylacrylate (5c)
White solid; yield: 72%; mp 148–150 °C.
Synthesis 2007, No. 6, 911–917 © Thieme Stuttgart · New York