3.4. Chemical Synthesis
A general procedure for the synthesis of α-
N,
N-dibenzylaminotrimethyl-silyloxycyanohydrines
2 and
3 is described below (see
Scheme 2).
A solution of (S)-2-(N,N-dibenzylamino)propanal 1 (17.3 mmol, 1 equiv) dissolved in 100 mL of anhydrous dichloromethane (DCM) was added to a 250 mL round bottom flask under nitrogen atmosphere, and ZnI2 (5.52 g, 17.3 mmol, 1 equiv) was added dropwise with stirring for 10 min. TMSCN (2.54 mL, 1.88 g, 19 mmol, 1.1 equiv) was added dropwise, and the resulting mixture was stirred for 2 h at 0 °C. Water (20 mL) was added and the mixture was stirred for 5 min and it was allowed to warm to 25 °C. The resulting mixture was extracted with DCM (50 mL) and the layers were separated. The aqueous layer was extracted with DCM (2 × 50 mL). The organic layers were combined and washed with brine (2 × 50 mL), dried over anhydrous sodium sulfate (Na2SO4), filtered, and the solvent was removed under vacuum to render the corresponding compound 3 as a colorless oil. In the case of the synthesis of silyloxycyanohydrines 2, MgBr2 (17.3 mmol, 1 equiv) was used as the catalyst of choice to obtain the desired product 2 as colorless oil.
(2S,3S)-3-(Dibenzylamino)-2-(trimethylsilyloxy) butanonitrile (2a). Colorless oil. (5.5 g, 13.8 mmol, 88%). IR (neat, cm−1): 3061, 2955, 2228, 1255, 1106, 848 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.34 (10H, m), 4.45 (1H, d, J = 5.8 Hz), 3.81 (2H, d, J = 13.8 Hz), 3.63 (2H, d, J = 13.8 Hz), 3.00 (1H, m), 1.75 (2H, m), 1.25 (1H, m), 0.90 (3H, d, J = 6.6 Hz), 0.70 (3H, d, J = 6.6 Hz). 13C NMR (50 MHz, CDCl3) δ 139.0, 128.6, 128.0, 126.8, 119.8, 63.2, 58.8, 54.6, 36.4, 25.0, 23.3, 22.0, 20.4.
(2R,3S)-3-(Dibenzylamino)-4-phenyl-2-(trimethylsilyloxy) butanonitrile (2b). Colorless oil. (3.8 g, 8.9 mmol, 95%). IR (neat, cm−1): 3029, 2951, 2367, 1255, 1113, 849 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.28 (15H, m), 4.48 (1H, d, J = 6.2 Hz), 3.72 (4H, br s), 3.38 (1H, dt, J = 8.0, 6.2 Hz), 3.04 (2H, m), 1.26 (9H, s). 13C NMR (50 MHz, CDCl3) δ 139.3, 138.7, 129.4, 128.8, 127.5, 127.0, 126.8, 126.3, 119.7, 64.2, 62.8, 55.2, 33.2, 1.9.
(2S,3S)-3-(Dibenzylamino)-4-methyl-2-(trimethylsilyloxy) hexanonitrile (2c). Colorless oil. (3.9 g, 9.9 mmol, 99%). IR (neat, cm−1): 3061, 2959, 2233, 1246, 1103, 846 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.33 (10H, m), 4.78 (1H, d, J = 4.8 Hz), 3.87 (2H, d, J = 13.6 Hz), 3.65 (2H, d, J = 13.6 Hz), 2.79 (1H, dd, J = 7.8, 4.8 Hz), 1.94 (2H, m), 1.17 (1H, m), 0.97 (3H, d, J = 7.0 Hz), 0.75 (3H, t, J = 7.4 Hz). 13C NMR (50 MHz, CDCl3) δ 139.1, 129.0, 128.2, 126.9, 120.3, 64.0, 61.0, 54.9, 33.0, 27.1, 16.0, 11.2, −0.2.
(2R,3S)-3-(Dibenzylamino)-5-methyl-2-(trimethylsilyloxy) hexanonitrile (2d). Colorless oil. (5.5 g, 13.8 mmol, 88%). IR (neat, cm−1): 3061, 2955, 2228, 1255, 1106, 848 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.34 (10H, m), 4.45 (1H, d, J = 5.8 Hz), 3.81 (2H, d, J = 13.8 Hz), 3.63 (2H, d, J = 13.8 Hz), 3.00 (1H, m), 1.75 (2H, m), 1.25 (1H, m), 0.90 (3H, d, J = 6.6 Hz), 0.70 (3H, d, J = 6.6 Hz). 13C NMR (50 MHz, CDCl3) δ 139.0, 128.6, 128.0, 126.8, 119.8, 63.2, 58.8, 54.6, 36.4, 25.0, 23.3, 22.0, 20.4.
(2R,3S)-3-(Dibenzylamino)-4-methyl-2-(trimethylsilyloxy) pentanonitrile (2e). Colorless oil. (3.9 g, 9.9 mmol, 99%). IR (neat, cm−1): 3062, 2957, 2218, 1250, 1085, 840 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.32 (10H, m), 4.77 (1H, d, J = 4.4 Hz), 4.19 (2H, d, J = 13.2 Hz), 3.73 (2H, d, J = 13.2 Hz), 2.66 (1H, dd, J = 10.6, 5.8 Hz), 2.15 (1H, m), 1.02 (3H, d, J = 6.6 Hz), 0.97 (3H, d, J = 6.6 Hz). 13C NMR (50 MHz, CDCl3) δ 138.9, 129.2, 128.5, 127.4, 119.9, 64.6, 59.3, 54.6, 28.9, 22.4, 20.1, −0.2.
(2S,3S)-3-(Dibenzylamino)-2-(trimethylsilyloxy) butanonitrile (3a). Colorless oil. (2.7 g, 8.9 mmol, 80%). IR (neat, cm−1): 3061, 2959, 2212, 1253, 1092, 845 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.43 (10H, m), 4.47 (1H, d, J = 8.8 Hz), 3.87 (2H, d, J = 13.6 Hz), 3.64 (2H, d, J = 13.6 Hz), 3.24 (1H, m), 1.24 (3H, d, J = 6.6 Hz). 13C NMR (50 MHz, CDCl3) δ 139.0, 128.8, 128.4, 127.2, 120.0, 65.2, 57.6, 55.1, 9.5, 0.08. ESI-MS, m/z: [M + H]+ 353; [M + Na]+ 375.
(2S,3S)-3-(Dibenzylamino)-4-phenyl-2-(trimethylsilyloxy) butanonitrile (3b). Colorless oil. (3.1 g, 8.7 mmol, 82%). IR (neat, cm−1): 3028, 2950, 2368, 1254, 1114, 850 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.22 (15H, m), 4.46 (1H, d, J = 6.2 Hz), 3.72 (4H, br s), 3.38 (1H, dt, J = 8.0, 6.2 Hz), 2.99 (2H, m), 0.17 (9H, s). 13C NMR (50 MHz, CDCl3) δ 138.9, 138.6, 129.1, 128.5, 128.0, 127.9, 126.8, 126.0, 119.5, 63.0, 62.7, 54.7, 33.1, −0.4. ESI-MS, m/z: [M + H]+ 429; MS/MS, m/z (rel. int.): 311(100), 210(20). ESI-MS, m/z: [M + Na]+ 451.
(2S,3S)-3-(Dibenzylamino)-4-methyl-2-(trimethylsilyloxy) hexanonitrile (3c). Colorless oil. (3.8 g, 9.8 mmol, 74%). IR (neat, cm−1): 3060, 2958, 2232, 1245, 1102, 845 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.33 (10H, m), 4.78 (1H, d, J = 4.8 Hz), 3.87 (2H, d, J = 13.6 Hz), 3.65 (2H, d, J = 13.6 Hz), 2.79 (1H, dd, J = 7.8, 4.8 Hz), 1.94 (2H, m), 1.17 (1H, m), 0.97 (3H, d, J = 7.0 Hz), 0.75 (3H, t, J = 7.4 Hz). 13C NMR (50 MHz, CDCl3) δ 139.1, 129.0, 128.2, 126.9, 120.3, 64.0, 61.0, 54.9, 33.0, 27.1, 16.0, 11.2, −0.2. ESI-MS, m/z: [M + H]+ 296; EM/EM m/z (rel. int.): 206(35), 181(95), 120(85), 91(100). EM-IES m/z: [M + H]+ 395, [M + Na]+ 417.
(2S,3S)-3-(Dibenzylamino)-5-methyl-2-(trimethylsilyloxy) hexanonitrile (3d). Colorless oil. (4.8 g, 12.6 mmol, 97%). IR (neat, cm−1): 3061, 2955, 2228, 1255, 1106, 848 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.34 (10H, m), 4.45 (1H, d, J = 5.8 Hz), 3.81 (2H, d, J = 13.8 Hz), 3.63 (2H, d, J = 13.8 Hz), 3.00 (1H, m), 1.75 (2H, m), 1.25 (1H, m), 0.90 (3H, d, J = 6.6 Hz), 0.70 (3H, d, J = 6.6 Hz). 13C NMR (50 MHz, CDCl3) δ 139.0, 128.6, 128.0, 126.8, 119.8, 63.2, 58.8, 54.6, 36.4, 25.0, 23.3, 22.0, 20.4. ESI-MS, m/z: [M + H]+ 395, [M + Na]+ 417, [M-Me + 2H]+ 381, MS/MS, m/z (rel. int.): 290(100), 248(10), 213(12), 157(10).
(2S,3S)-3-(Dibenzylamino)-4-methyl-2-(trimethylsilyloxy) pentanonitrile (3e). Colorless oil. (6.0 g, 15.2 mmol, 96%). IR (neat, cm−1): 3062, 2957, 2218, 1250, 1085, 840 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.32 (10H, m), 4.77 (1H, d, J = 4.4 Hz), 4.19 (2H, d, J = 13.2 Hz), 3.73 (2H, d, J = 13.2 Hz), 2.66 (1H, dd, J = 10.6, 5.8 Hz), 2.15 (1H, m), 1.02 (3H, d, J = 6.6 Hz), 0.97 (3H, d, J = 6.6 Hz). 13C NMR (50 MHz, CDCl3) δ 138.9, 129.2, 128.5, 127.4, 119.9, 64.6, 59.3, 54.6, 28.9, 22.4, 20.1, −0.2. ESI-MS, m/z: [M-Me + 2H]+ 367, MS/MS, m/z (rel. int.): 325(95), 275(100), 199(10).
A general procedure for the synthesis of the α-
N,
N-dibenzylaminoaminoalcohols
4 and
5 is described below (see
Scheme 3).
LiAlH4 (2.0 equiv) was added to a solution of a trimetylsilyloxycianohydrine 3a in anhydrous Et2O under argon atmosphere at 0 °C and the resulting mixture was stirred for 4 h at the same temperature. An aqueous solution of 5% potassium hydroxide (KOH) was added dropwise to the reaction mixture and a white solid was obtained. The resulting mixture was filtered and the solvent was removed under vacuum to obtain a crude oil.
(2S,3S)-1-Amino-3-(dibenzylamino)-2-butanol (4a). Colorless oil. (1.59 g, 5.1 mmol, 47%). IR (neat, cm−1): 3363, 3284, 3027, 2958, 1578, 1076 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.25 (10H, m), 3.65 (2H, d, J = 13.6 Hz), 3.62 (1H, dd, J = 11.0, 5.8 Hz), 3.43 (1H, m), 3.31 (2H, d, J = 13.6 Hz), 2.76 (1H, dd, J = 11.0, 6.4 Hz), 2.55 (1H, q, J = 6.6 Hz), 1.10 (3H, d, J = 6.6 Hz). 13C NMR (50 MHz, CDCl3) δ 140.0, 129.1, 128.6, 127.2, 72.0, 66.0, 54.3, 44.7, 15.4.
(2S,3S)-1-Amino-3-(dibenzylamino)-4-phenyl-2-butanol (4b). Colorless oil. (3.4 g, 9.6 mmol, 94%). IR (neat, cm−1): 3367, 3298, 2924, 1603, 1252, 1109 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.21 (15H, m), 3.93 (1H, dd, J = 13.4, 9.4 Hz), 3.70 (2H, d, J = 13.6 Hz), 3.57 (2H, d, J = 13.6 Hz), 3.43 (1H, dd, J = 15.0, 13.4, Hz), 2.82 (4H, m). 13C NMR (50 MHz, CDCl3) δ 141.1, 139.5, 129.1, 128.5, 128.2, 127.9, 126.6, 125.5, 72.0, 61.4, 54.4, 44.6, 32.5.
(2S,3S,4S)-1-Amino-3-(dibenzylamino)-4-methyl-2-hexanol (4c). Colorless oil. (2.3 g, 7 mmol, 72%). IR (neat, cm−1): 3345, 3289, 3060, 2955, 1601, 1376, 1061, 1027 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.24 (10H, m), 3.75 (2H, d, J = 13.2 Hz), 3.73 (2H, m), 3.54 (2H, d, J = 13.2 Hz), 2.65 (1H, dd, J = 13.6, 7.0 Hz), 2.44 (1H, dd, J = 7.6, 4.6 Hz), 2.24 (1H, m), 1.90 (1H, m), 1.65 (1H, m), 1.08 (3H, d, J = 6.6 Hz), 0.95 (3H, t, J = 7.6 Hz). 13C NMR (50 MHz, CDCl3) δ 139.7, 128.8, 128.0, 126.8, 70.1, 62.5, 54.8, 44.6, 32.4, 29.8, 16.1, 12.2.
(2S,3S)-1-Amino-3-(dibenzylamino)-5-methyl-2-hexanol (4d). Colorless oil. (3.05 g, 6.5 mmol, 50%) IR (neat, cm−1): 3302, 3062, 2952, 1601, 1366, 1072 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.30 (10H, m), 3.76 (1H, m), 3.62 (4H, br s), 3.38 (1H, dd, J = 13.2, 11.8 Hz), 2.66 (3H, m), 1.60 (1H, m), 0.91 (3H, d, J = 6.6 Hz), 0.73 (3H, d, J = 6.4 Hz). 13C NMR (50 MHz, CDCl3) δ 139.9, 128.7, 127.9, 126.6, 71.4, 56.8, 54.6, 44.9, 35.5, 25.2, 23.2, 22.7.
(2S,3S)-1-Amino-3-(dibenzylamino)-4-methyl-2-pentanol (4e). Colorless oil. (1.5 g, 4.8 mmol, 88%) IR (neat, cm−1): 3342, 3283, 3061, 2955, 1601, 1361, 1068 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.24 (10H, m), 3.87 (2H, d, J = 13.2 Hz), 3.66 (2H, d, J = 13.2 Hz), 3.56 (1H, dd, J = 10.6, 4.8 Hz), 3.42 (1H, t, J = 10.6 Hz), 2.52 (1H, m), 2.06 (1H, m), 1.12 (3H, d, J = 6.6 Hz), 0.87 (1H, d, J = 7.0 Hz). 13C NMR (50 MHz, CDCl3) δ 139.0, 129.2, 128.2, 127.3, 69.1, 64.2, 54.2, 46.2, 26.4, 23.6, 19.6.
(2R,3S)-1-Amino-3-(dibenzylamino)-2-butanol (5a). Colorless oil. (3.3 g, 11.5 mmol, 76%). IR (neat, cm−1): 3363, 3284, 3027, 2958, 1578, 1076 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.25 (10H, m), 3.65 (2H, d, J = 13.6 Hz), 3.62 (1H, dd, J = 11.0, 5.8 Hz), 3.43 (1H, m), 3.31 (2H, d, J = 13.6 Hz), 2.76 (1H, dd, J = 6.4, 11.0 Hz), 2.55 (1H, q, J = 6.6 Hz), 1.10 (3H, d, J = 6.6 Hz). 13C NMR (50 MHz, CDCl3) δ 140.3, 129.1, 128.5, 127.2, 73.5, 65.6, 54.7, 44.6, 12.1. ESI-MS, m/z: [M + H]+ 286; MS/MS, m/z (rel. Int.): 268(100), 199(5), 91(10).
(2R,3S)-1-Amino-3-(dibenzylamino)-4-phenyl-2-butanol (5b). Colorless oil. (3.4 g, 9.6 mmol, 94%). IR (neat, cm−1): 3365, 3299, 2926, 1600, 1251, 1110 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.21 (15H, m), 3.93 (1H, dd, J = 13.4, 9.4 Hz), 3.70 (2H, d, J = 13.6 Hz), 3.57 (2H, d, J = 13.6 Hz), 3.43 (1H, dd, J = 15.0, 13.4 Hz), 2.82 (4H, m). 13C NMR (50 MHz, CDCl3) δ 141.1, 139.5, 129.1, 128.5, 128.2, 127.9, 126.6, 125.5, 72.0, 61.4, 54.4, 44.6, 32.5. ESI-MS, m/z: [M + H]+ 361; MS/MS, m/z (rel. int.): 344(98), 300(20), 210(100).
(2R,3S)-1-Amino-3-(dibenzylamino)-4-methyl-2-hexanol (5c). Colorless oil. (2.4 g, 7.35 mmol, 79%). IR (neat, cm−1): 3345, 3289, 3060, 2955, 1601, 1376, 1061, 1027 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.24 (10H, m), 3.75 (2H, d, J = 13.2 Hz), 3.73 (2H, m), 3.54 (2H, d, J = 13.2 Hz), 2.65 (1H, dd, J = 13.6, 7.0 Hz), 2.44 (1H, dd, J = 7.6, 4.6 Hz), 2.24 (1H, m), 1.90 (1H, m), 1.65 (1H, m), 1.08 (3H, d, J = 6.6 Hz), 0.95 (3H, t, J = 7.6 Hz). 13C NMR (50 MHz, CDCl3) δ 139.7, 128.8, 128.0, 126.8, 70.1, 62.5, 54.8, 44.6, 32.4, 29.8, 16.1, 12.2. ESI-MS, m/z: [M + H]+ 327; MS/MS m/z (rel. int.): 309(100), 292(10), 198(35), 91(5).
(2R,3S)-1-Amino-3-(dibenzylamino)-5-methyl-2-hexanol (5d). Colorless oil. (3.05 g, 6.5 mmol, 50%). IR (neat, cm−1): 3300, 3061, 2952, 1601, 1366, 1072 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.30 (10H, m), 3.76 (1H, m), 3.62 (4H, br s), 3.38 (1H, dd, J = 13.2, 11.8 Hz), 2.66 (3H, m), 1.60 (1H, m), 0.91 (3H, d, J = 6.6 Hz), 0.73 (3H, d, J = 6.4 Hz). 13C NMR (50 MHz, CDCl3) δ 139.9, 128.7, 127.9, 126.6, 71.4, 56.8, 54.6, 44.9, 35.5, 25.2, 23.2, 22.7. ESI-MS, m/z: [M + H]+ 327; MS/MS, m/z (rel.int.): 310(100), 233(45), 198(30).
(2R,3S)-1-Amino-3-(dibenzylamino)-4-methyl-2-pentanol (5e). Colorless oil. (2.8 g, 8.7 mmol, 60%). IR (neat, cm−1): 3342, 3283, 3061, 2955, 1601, 1361, 1068 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.24 (10H, m), 3.87 (2H, d, J = 13.2 Hz), 3.66 (2H, d, J = 13.2 Hz), 3.56 (1H, dd, J = 10.6, 4.8 Hz), 3.42 (1H, t, J = 10.6 Hz), 2.52 (1H, m), 2.06 (1H, m), 1.12 (3H, d, J = 6.6 Hz), 0.87 (1H, d, J = 7.0 Hz). 13C NMR (50 MHz, CDCl3) δ 139.5, 128.9, 128.0, 126.8, 70.5, 64.0, 55.1, 44.7, 26.3, 23.6, 20.1. ESI-MS, m/z: [M + H]+ 313; MS/MS, m/z (rel. int.): 296(100), 278(5), 199(10), 91(7).
A general procedure for the synthesis of 1,3-oxazolidin-2-ones
6 and
7 is described below (see
Scheme 4).
α-N,N-dibencilaminoaminoalcohol 5a (3.0 g, 10.4 mmol) was dissolved in anhydrous DCM (100 mL). A solution of triphosgene (1 equiv) in anhydrous DCM was added dropwise to the aminoalcohol 5a solution at 0 °C. The reaction mixture was stirred for 8 h, followed by addition of saturated sodium bicarbonate (NaHCO3) and the resulting mixture was stirred for an additional 30 min. The mixture was extracted with DCM (3 × 20 mL). The organic layers were combined, and it was dried with anhydrous Na2SO4, filtered and the solvent was removed under vacuum. The residue was purified by column chromatography over silica gel to afford the desired product.
(S)-5-((S)-1-(Dibenzylamino)ethyl)oxazolidin-2-one (6a). Light brown solid. (2.3 g, 6.6 mmol, 99%). IR (neat, cm−1, KBr): 3277, 2961, 1752, 1237, 1077 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.27 (10H, m), 5.49 (1H, br s), 4.86 (1H, q, J = 8.4 Hz), 3.73 (2H, d, J = 13.6 Hz), 3.66 (1H, t, J = 8.4 Hz), 3.48 (2H, d, J = 13.6 Hz), 3.26 (1H, t, J = 8.4 Hz), 2.66 (1H, dd, J = 9.0, 1.6 Hz), 2.03 (1H, m), 1.44 (2H, m), 1.14 (3H, d, J = 7.0 Hz), 0.93 (3H, t, J = 7.2 Hz). 13C NMR (50 MHz, CDCl3) δ 159.9, 139.2, 129.0, 128.4, 127.3, 75.4, 63.6, 53.7, 44.7, 30.7, 30.0, 14.6, 11.4.
(S)-5-((S)-1-(Dibenzylamino)-2-phenylethyl)oxazolidin-2-one (6b). Light brown solid. (2.5 g, 6.4 mmol, 89%). IR (neat, cm−1, KBr): 3283, 3026, 2931, 1754, 1368, 1240 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.21 (15H, m), 5.91 (1H, br s), 4.80 (1H, m), 3.62 (4H, br s), 3.52 (1H, t, J = 8.8 Hz), 3.08 (1H, t, J = 8.8 Hz), 3.06 (3H, br s). 13C NMR (50 MHz, CDCl3) δ 159.6, 139.5, 138.8, 129.3, 128.4, 128.1, 128.0, 127.9, 126.8, 126.0, 76.8, 62.4, 54.4, 44.8, 32.4.
(5S)-5-((1S)-1-(Dibenzylamino)-2-methylbutyl)oxazolidin-2-one (6c). Colorless oil. (2.11 g, 5.9 mmol, 84%). IR (neat, cm−1, KBr): 3277, 2961, 1752, 1237, 1077 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.27 (10H, m), 5.49 (1H, br s), 4.86 (1H, q, J = 8.4 Hz), 3.73 (2H, d, J = 13.6 Hz), 3.66 (1H, t, J = 8.4 Hz), 3.48 (2H, d, J = 13.6 Hz), 3.26 (1H, t, J = 8.4 Hz), 2.66 (1H, dd, J = 9.0, 1.6 Hz), 2.03 (1H, m), 1.44 (2H, m), 1.14 (3H, d, J = 7.0 Hz), 0.93 (3H, t, J = 7.2 Hz). 13C NMR (50 MHz, CDCl3) δ 159.9, 139.2, 129.0, 128.4, 127.3, 75.4, 63.6, 54.7, 45.7, 31.7, 30.0, 15.6, 12.4.
(S)-5-((S)-1-(Dibenzylamino)-3-methylbutyl)-1,3-oxazolidin-2-one (6d). Colorless oil (3.5 g, 9.8 mmol, 90%). IR (neat, cm−1, KBr): 3277, 3028, 1753, 1240, 1080 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.27 (10H, m), 6.09 (1H, br s), 4.75 (1H, m), 3.72 (2H, d, J = 13.8 Hz), 3.58 (1H, t, J = 8.4 Hz), 3.55 (2H, d, J = 13.8 Hz), 3.12 (1H, t, J = 8.4 Hz), 2.67 (1H, dd, J = 7.0, 5.6 Hz), 1.96 (1H, heptet, J = 6.6 Hz), 1.73 (6H, q, J = 7.0 Hz), 1.27 (1H, m), 0.92 (3H, d, J = 6.6 Hz), 0.73 (3H, d, J = 6.2 Hz).13C NMR (50 MHz, CDCl3) δ 160.3, 140.1, 129.4, 128.4, 127.1, 78.9, 57.0, 55.0, 43.9, 35.6, 24.5, 23.4, 22.4.
(S)-5-((S)-1-(Dibenzylamino)-2-methylpropyl)-1,3-oxazolidin-2-one (6e). Light brown solid. (1.5 g, 4.4 mmol, 50%). IR (neat, cm−1, KBr): 3277, 3028, 1753, 1240, 1080 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.27 (10H, m), 6.09 (1H, br s), 4.75 (1H, m), 3.72 (2H, d, J = 13.8 Hz), 3.58 (1H, t, J = 8.4 Hz), 3.55 (2H, d, J = 13.8 Hz), 3.12 (1H, t, J = 8.4 Hz), 2.67 (1H, dd, J = 7.0, 5.6 Hz), 1.96 (1H, heptet, J = 6.6 Hz), 1.73 (6H, q, J = 7.0 Hz), 1.27 (1H, m), 0.92 (3H, d, J = 6.6 Hz), 0.73 (3H, d, J = 6.2 Hz). 13C NMR (50 MHz, CDCl3) δ 160.1, 139.9, 129.4, 128.3, 127.0, 73.4, 63.6, 56.1, 44.0, 28.2, 21.4, 19.1.
(R)-5-((S)-1-(Dibenzylaminoethyl)-1,3-oxazolidin-2-one (7a). Light brown solid. (2.7 g, 8.6 mmol, 85%).
(c 1.00, CHCl3). Pf = 95 °C. Rf = 0.48 (ethyl acetate/petroleum ether: 1/1). IR (neat, cm−1, KBr): 3254, 2826, 1748, 1239 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.25 (10H, m), 5.73 (1H, br s), 4.83 (1H, q, J = 8.6 Hz), 3.67 (2H, d, J = 13.4 Hz), 3.62 (1H, t, J = 8.6 Hz), 3.55 (2H, d, J = 13.4 Hz), 3.23 (1H, t, J = 8.6 Hz), 2.58 (1H, dd, J = 8.6, 3.2 Hz), 3.33 (1H, m), 1.11 (6H, t, J = 7.4 Hz). 13C NMR (50 MHz, CDCl3) δ 159.7, 138.8, 128.7, 128.1, 127.0, 78.3, 56.5, 54.4, 44.7, 8.6. ESI-MS, m/z: [M + H]+ 311; MS/MS m/z (rel. int.): 250(50), 219(100), 181(93), 91(60). HPLC: 0.8 mL/min; 70:30 MeOH/H2O; Rt: 5.8 min.
(R)-5-((S)-1-(Dibenzylamino)-2-phenylethyl)oxazolidin-2-one (7b). Light brown solid. (2.5 g, 6.4 mmol, 89%).
(c 1.00, CHCl3). Pf = 102 °C. Rf = 0.50 (ethyl acetate/petroleum ether: 1/1). IR (neat, cm−1, KBr): 3283, 3026, 2931, 1754, 1368, 1240 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.21 (15H, m), 5.91 (1H, br s), 4.80 (1H, m), 3.62 (4H, br s), 3.52 (1H, t, J = 8.8 Hz), 3.08 (1H, t, J = 8.8 Hz), 3.06 (3H, br s). 13C NMR (50 MHz, CDCl3) δ 159.6, 139.5, 138.8, 129.3, 128.4, 128.1, 128.0, 127.9, 126.8, 126.0, 76.8, 62.4, 54.4, 44.8, 32.4. ESI-MS, m/z: [M + H]+ 387; MS/MS m/z (rel. int.): 326(75), 295(100), 181(40). HPLC: 0.8 mL/min; 70:30 MeOH/H2O; Rt: 6.3 min.
(5R)-5-((1S)-1-(Dibenzylamino)-2-methylbutyl)oxazolidin-2-one (7c). Light brown solid. (2.3 g, 6.6 mmol, 99%).
(c 1.00, CHCl3). Pf = 42 °C. Rf = 0.62 (ethyl acetate/petroleum ether: 1/1). IR (neat, cm−1, KBr): 3277, 2961, 1752, 1237, 1077 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.27 (10H, m), 5.49 (1H, br s), 4.86 (1H, q, J = 8.4 Hz), 3.73 (2H, d, J = 13.6 Hz), 3.66 (1H, t, J = 8.4 Hz), 3.48 (2H, d, J = 13.6 Hz), 3.26 (1H, t, J = 8.4 Hz), 2.66 (1H, dd, J = 9.0, 1.6 Hz), 2.03 (1H, m), 1.44 (2H, m), 1.14 (3H, d, J = 7.0 Hz), 0.93 (3H, t, J = 7.2 Hz). 13C NMR (50 MHz, CDCl3) δ 159.9 (C), 139.2, 129.0, 128.4, 127.3, 75.4, 63.6, 54.7, 45.7, 31.7, 30.0, 15.6, 12.4. ESI-MS, m/z: [M + H]+ 353; MS/MS, m/z (rel. int.): 283(100), 202(45). HPLC: 0.8 mL/min; 70:30 MeOH/H2O; Rt: 8.4 min.
(R)-5-((S)-1-(Dibenzylamino)-3-methylbutyl)-oxazolidin-2-one (7d). Light brown solid. (1.5 g, 4.4 mmol, 50%).
(c 1.00, CHCl3). Pf = 43 °C. Rf = 0.52 (ethyl acetate/petroleum ether: 1/1). IR (neat, cm−1, KBr): 3277, 3028, 1753, 1240, 1080 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.27 (10H, m), 6.09 (1H, br s), 4.75 (1H, m), 3.72 (2H, d, J = 13.8 Hz), 3.58 (1H, t, J = 8.4 Hz), 3.55 (2H, d, J = 13.8 Hz), 3.12 (1H, t, J = 8.4 Hz), 2.67 (1H, dd, J = 7.0, 5.6 Hz), 1.96 (1H, heptet, J = 6.6 Hz), 1.73 (6H, q, J = 7.0 Hz), 1.27 (1H, m), 0.92 (3H, d, J = 6.6 Hz), 0.73 (3H, d, J = 6.2 Hz). 13C NMR (50 MHz, CDCl3) δ 159.9, 139.2, 128.6, 128.0, 126.9, 76.8, 58.2, 54.4, 44.9, 35.1, 24.7, 23.3, 22.4. ESI-MS, m/z: [M + H]+ 353; MS/MS m/z (rel. int.): 261(100), 202(75), 181(80). HPLC: 0.8 mL/min; 70:30 MeOH/H2O; Rt: 6.8 min.
(R)-5-((S)-1-(Dibenzylamino)-2-methylpropyl)oxazolidin-2-one (7e). Light brown solid. (1.5 g, 4.0 mmol, 85%).
(c 1.00, CHCl3). Pf = 45 °C. Rf = 0.55 (ethyl acetate/petroleum ether: 1/1). IR (neat, cm−1, KBr): 3284, 2958, 1752, 1239, 1078 cm−1. 1H NMR (200 MHz, CDCl3) δ 7.25 (10H, m), 5.73 (1H, br s), 4.83 (1H, q, J = 8.6 Hz), 3.67 (2H, d, J = 13.4 Hz), 3.62 (1H, t, J = 8.6 Hz), 3.55 (2H, d, J = 13.4 Hz), 3.23 (1H, t, J = 8.6 Hz), 2.58 (1H, dd, J = 8.6, 3.2 Hz), 3.33 (1H, m), 1.11 (6H, t, J = 7.4 Hz). 13C NMR (50 MHz, CDCl3) δ 159.7, 138.8, 128.7, 128.1, 127.0, 75.4, 64.1, 54.6, 45.5, 25.1, 23.3, 19.0. ESI-MS, m/z: [M + H]+ 339; MS/MS, m/z (rel.int.): 283(100), 247(40), 188(45). HPLC: 0.8 mL/min; 70:30 MeOH/H2O; Rt: 5.8 min.