Molecules 2008, 13
345
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s, 1H), 2.60-2.75 (m, 2H), 2.88 (m, 1H), 3.68 (s, 3H), 3.79 (s, 2H), 7.20-7.45 (m, 5H); C-NMR (50
MHz) δ 15.5, 40.1, 51.8, 52.2, 53.8, 127.0, 128.1, 128.4, 140.1, 176.3.
Methyl 3-(benzylamino)propanoate (3c) and bis [Methyl 3-(benzylamino)]propanoate (6)
Prepared from benzylamine (1, 0.10 g, 1 mmol), methyl acrylate (2c, 0.09 g, 1 mmol), and methanol
(3 mL). The reaction was heated at 115 °C, 59 psi for 3 hr, to afford a 1:1 mixture of the compounds
3c-6, which were purified by column chromatography on silica, eluting with hexane-ethyl acetate
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(8:2). Compound 3c: H-NMR (200 MHz) δ 1.82 (br s, 1H), 2.54 (t, J = 6.6 Hz, 2H), 2.89 (t, J = 6.4
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Hz, 2H), 3.67 (s, 3H), 3.80 (s, 2H), 7.29-7.42 (m, 5H); C-NMR (50 MHz) δ 34.7, 44.6, 51.8, 53.9,
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127.0, 128.1, 128.5, 140.0, 173.2. Compound 6: H-NMR (200 MHz) δ 2.47 (t, J = 7.0 Hz, 4H), 2.80
(t, J = 7.2 Hz, 4H), 3.58 (s, 2H), 3.64 (s, 6H), 7.20-7.35 (m, 5H); 13C-NMR (50 MHz) δ 32.7, 48.8,
49.3, 49.7, 51.5, 51.9, 58.4, 128.0, 128.2, 128.5, 129.0, 139.9, 172.9.
Methyl N-α-Methylbenzylaminobutanoate (5a)
(S)-(-)-α-methylbenzylamine (4, 0.12 g, 1 mmol), methyl crotonate (2a, 0.10 g, 1 mmol) and
methanol (3 mL) were heated at 150 °C and 71 psi for and 6 hr, according to the general procedure and
then concentrated on a rotatory evaporator, providing 5a (0.16 g, 74 % yield) as a ca. 1:1 mixture of
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diastereomers (according to the H-NMR spectrum in CDCl3). Separation of the mixture was
accomplished by gradient flash chromatography (eluent: hexane-ethyl acetate, 19:2 to 1:1) to yield
pure fractions of (αS,3S)-5a and (αS,3R)-5a. (S,3S)-5a: [α]D = -45.5 (c = 1.1, CHCl3) [lit.[13] [α]D = -
37.6 (c = 0.98, CHCl3)]; 1H-NMR (400 MHz) δ 1.05 (d, J = 12.4 Hz, 3H), 1.32 (d, J = 13.2 Hz, 3H),
1.65 (br s, 1H), 2.41 (t, J = 6.6 Hz, 2H), 2.96 (m, 1H), 3.65 (s, 3H), 3.87 (q, J = 12.4 Hz, 1H), 7.19-7.4
(m, 5H); 13C-NMR (100 MHz) δ 21.7, 24.8, 40.8, 47.9, 51.6, 55.43, 126.6, 127.0, 128.5, 146.0, 172.7;
(S,3R)-5a: [α]D = -49.5 (c =1.2, CHCl3) [lit. [13] [α]D = -41.0 (c = 1.31, CHCl3)]; 1H-NMR (400 MHz)
δ 1.03 (d, J = 6.4 Hz, 3H), 1.30 (d, J = 6.4 Hz, 3H), 2.2 (br s, 1H), 2.30 (m, 2H), 2.83 (m, 1H), 3.60 (s,
3H), 3.87 (q, J = 6.8 Hz, 1H), 7.2-7.4 (m, 5H); 13C-NMR (100 MHz) δ 20.0, 25.3, 42.3, 47.2, 51.6,
55.1, 126.7, 127.0, 128.5, 145.3, 172.8.
Methyl N-α-methylbenzyl-3-amino-2-methylpropionate (5b)
(S)-(-)-α-Methylbenzylamine (4, 0.12 g, 1 mmol), methyl methacrylate (2b, 0.10 g, 1 mmol) and
methanol (3 mL) were heated at Ti = 130 °C, 100 psi for 6 hr, and then Tf = 150 °C during 3 h.
Concentration of the mixture on a rotatory evaporator gave 5b (0.15 g, 70 % yield) as a ca. 44:56,
mixture of diasteromers (according to the 1H-NMR spectrum in CDCl3) that was separated by gradient
flash chromatography (eluent: hexane-ethyl acetate, 90:10 to 50:50) to yield pure fractions of (αS,2S)-
5b and (αS,2R)-5b. (αS,2S)-5b [α]D = -22.6 (c =2.3, CHCl3). [lit.[14] [α]D = -24.7 (c = 2.3, CHCl3)];
1H-NMR (200 MHz) δ 1.13 (d, J = 6.6 Hz, 3H), 1.32 (d, J = 6.6 Hz, 3H), 1.77 (br s, 1H), 2.45 (dd, J =
11.1 Hz, J = 5.2 Hz, 1H), 2.59 (m, 1H), 2.77 (dd, J = 11.1 Hz, J = 7.6 Hz, 1H), 3.70 (s, 3H), 3.77 (m,
1H), 7.19-7.35 (m, 5H); 13C-NMR (50 MHz) δ 15.5, 24.7, 40.4, 50.8, 51.8, 58.4, 126.7, 126.9, 128.5,
145.7, 176.4. (αS,2R)-5b. [α]D = -54.0 (c = 2.1, CHCl3) [lit. [14] [α]D = -56.1 (c = 2, CHCl3); 1H-NMR