Helvetica Chimica Acta Vol. 85 (2002)
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6.0, 14.0, 1 H, indole-CH2); 4.01 4.06 (m, 1 H, OCH2CH); 4.15 (dd, J 2.7, 9.1, 1 H, OCH2CH); 4.33 (ddd, J
2.7, 3.7, 8.4, NCH); 4.59 4.68 (m, C(O)CH); nA 5.02, nB 5.06 (AB, J 12.3, PhCH2); 7.19 7.35 (m, 7 ar-
om. H); 7.43 (s, 1 arom. H); 7.74 (ddd, J 0.7, 1.3, 7.7, 1 arom. H); 8.11 (br. d, J 8.0, arom. NCH). 13C-NMR
(100 MHz, CDCl3): 14.5, 18.0 (Me); 27.3 (CH2); 28.2 (CH); 28.2 (Me); 35.8 (CH2); 39.7, 58.9 (CH); 63.2, 66.5
(CH2); 83.6 (C); 115.1 (CH); 116.7 (C); 119.5, 122.7, 124.5, 124.5, 128.2, 128.2, 128.5 (CH); 130.1, 135.5, 135.7,
149.6, 153.6, 171.7, 175.0 (C). HR-MALDI-MS: 571.2421 (1.05 ppm) (C31H36N2O7Na ; calc. 571.2415). Anal.
calc. for C31H36N2O7 (548.63): C 67.87, H 6.61, N 5.11; found: C 67.88, H 6.59, N 5.11.
Benzyl (R)-3-({1-[(tert-Butoxy)carbonyl]-1H-indol-3-yl}methyl)-4-[(S)-4-isopropyl-5,5-diphenyl-2-oxo-
oxazolidin-3-yl]-4-oxobutanoate (9b). Analogously to the preparation of 9a, 8b (534 mg, 0.966 mmol) was
reacted. FC (pentane/Et2O 10 :1 to 6 :1) yielded 9b (608mg, 89%). White solid. M.p. 77 79 8. [a]rD:t: À102.9
(c 0.75, CHCl3). IR (CHCl3): 3036m, 2982m, 2933m, 1780s, 1727s, 1606w, 1494w, 1452s, 1370s, 1319m, 1085s,
1
1053w, 1019w, 1002w, 939w. H-NMR (400 MHz, CDCl3): 0.83 (d, J 6.7, Me); 0.89 (d, J 7.0, Me); 1.65 (s, t-
Bu); 1.95 2.03 (m, Me2CH); 2.29 (dd, J 10.4, 14.2, 1 H, indole-CH2); 2.39 (dd, J 4.1, 17.2, 1 H, C(O)CH2);
2.55 (ddd, J 1.0, 4.8, 14.2, 1 H, indole-CH2); 2.89 (dd, J 10.7, 17.2, 1 H, C(O)CH2); 4.51 4.61 (m, C(O)CH);
nA 4.99, nB 5.06 (AB, J 12.3, PhCH2); 5.39 (d, J 3.1, NCH); 7.16 7.47 (m, 18arom. H); 7.62 7.65
(m, 1 arom. H); 8.06 (br. d, J 7.8, arom. NCH). 13C-NMR (100 MHz, CDCl3): 16.1, 21.5 (Me); 26.7 (CH2);
28.2 (Me); 30.0 (CH); 35.2 (CH2); 39.3, 65.2 (CH); 66.5 (CH2); 83.5, 89.5 (C); 115.1 (CH); 116.5 (C); 119.5,
122.7, 124.2, 124.4, 125.4, 125.9, 128.0, 128.2, 128.3, 128.4, 128.5, 128.6, 128.6, 128.8 (CH); 130.0, 135.4, 135.7,
138.0, 142.3, 149.5, 153.0, 171.7, 174.7 (C). HR-MALDI-MS: 723.3039 (À0.28ppm) (C 43H44N2O7Na ; calc.
723.3041). Anal. calc. for C43H44N2O7 (700.83): C 73.69, H 6.33, N 4.00; found: C 73.70, H 6.54, N 3.92.
(R)-3-({1-[(tert-Butoxy)carbonyl]-1H-indol-3-yl}methyl)-4-[(S)-4-isopropyl-2-oxooxazolidin-3-yl]-4-oxo-
butyric Acid (10). The soln. of 9a (6.436 g, 11.731 mmol) in THF (130 ml) was stirred under H2 (1 atm., ballon)
in the presence of 10% Pd/C (510 mg) for 4 h. Pd/C was filtered off, washed with THF, and filtrate was
concentrated in vacuo to yield an oil. Et2O was added and evaporated in vacuo to yield 10 (5.838 g, quant.; pure
by 1H-NMR) as a white solid. An anal. sample was obtained by recrystallization from cyclohexane/AcOEt. M.p.
144 1458. IR (CHCl3): 2974m, 1779s, 1726s, 1453s, 1386s, 1360s, 1308m, 1158s, 1085m, 1057w, 1018w, 98 4w, 946w.
1H-NMR (400 MHz, CDCl3): 0.85 (d, J 6.9, Me); 0.88 (d, J 7.0, Me); 1.66 (s, t-Bu); 2.29 2.38( m, Me2CH);
2.46 (dd, J 3.9, 17.8, 1 H, C(O)CH2); 2.70 (dd, J 9.7, 14.0, 1 H, indole-CH2); 2.96 (dd, J 11.0, 17.8, 1 H,
C(O)CH2); 3.13 3.18( m, 1 H, indole-CH2); 4.05 (t, J 8.8, 1 H, CH2O); 4.16 (dd, J 2.7, 9.0, 1 H, CH2O); 4.33
(m, NCH); 4.53 4.61 (m, C(O)CH); 7.22 7.27 (m, 1 arom. H); 7.28 7.33 ( m, 1 arom. H); 7.44 (s, 1 arom. H);
7.73 7.76 (m, 1 arom. H); 8.11 (br. d, J 7.6, arom. NCH). 13C-NMR (100 MHz, CDCl3): 14.1, 17.9 (Me); 27.3
(CH2); 27.9 (CH); 28.2 (Me); 35.3 (CH2); 39.3, 58.8 (CH); 63.1 (CH2); 83.7 (C); 115.2 (CH); 116.4 (C); 119.4,
122.7, 124.5, 124.5 (CH); 130.1, 135.5, 149.6, 153.6, 175.6, 177.6 (C). HR-MALDI-MS: 481.1943 (À0.42 ppm)
(C24H30N2O7Na ; calc. 481.1945). Anal. calc. for C24H30N2O7 (458.50): C 62.87, H 6.59, N 6.11; found: C 62.84,
H 6.60, N 6.14.
(R)-3-({(3R/S)-1-[(tert-Butoxy)carbonyl]-2,3-dihydro-1H-indol-3-yl}methyl)-4-[(S)-4-isopropyl-2-oxo-
oxazolidin-3-yl]-4-oxobutyric Acid (11). The soln. of 9a (1.116 g, 2.034 mmol) in MeOH (20 ml) and THF
(20 ml) was stirred under H2 (1 atm, balloon) in the presence of 10% Pd/C (113 mg) at 08 to r.t. for 13 h. Pd/C
was filtered off, washed with THF and MeOH, and concentrated in vacuo. FC (pentane/Et2O/AcOH
200 :100 :1) yielded 11 (787 mg, 84%) as a mixture of epimers. White solid. 13C-NMR (100 MHz, CDCl3): 14.2,
14.3, 17.9, 18.0 (Me); 27.9, 28.0 (CH); 28.4, 28.5 (Me); 36.6 (CH); 37.0, 43.3, 52.6, 54.2 (CH2); 58.7, 58.8 (CH);
63.0, 63.1, 64.3 (CH2); 81 (C); 114.7, 114.8, 122.1, 122.3, 124.1, 128.0, 128.1, 128.2, 129.0 (CH); 134, 143, 152.5,
153.4, 153.5, 174.9, 175.1, 177.0 (C). HR-MALDI-MS: 483.2095 (À1.45 ppm) (C24H32N2O7Na ; calc. 483.2102).
Anal. calc. for C24H32N2O7 (460.52): C 62.59, H 7.00, N 6.08; found: C 62.55, H 7.01, N 5.91.
(S)-3-[(2R)-2-({[(Benzyloxy)carbonyl]amino}methyl)-3-{1-[(tert-butoxy)carbonyl]indol-3-yl}-1-oxo-
propyl]-4-isopropyloxazolidin-2-one (12). a) To a stirred soln. of 10 (419 mg, 0.913 mmol) in toluene (5 ml),
Et3N (0.25 ml, 1.79 mmol, 2 equiv.), diphenylphosphoryl azide ((PhO)2P(O)N3 ; 0.24 ml, 1.114 mmol,
1.2 equiv.), and BnOH (0.19 ml, 1.84 mmol, 2 equiv.) were added, and the mixture was stirred for 1 h at r.t.,
followed by refluxing for additional 1 h. Toluene was evaporated in vacuo, the residue was dissolved in Et2O
(30 ml) and 2m HCl (20 ml). The org. phase was separated, washed with sat. NaHCO3, dried (MgSO4), and
concentrated in vacuo. FC (CH2Cl2/Et2O 50 :1) yielded 12 (380 mg, 74%).
b) To a stirred soln. of the epimeric acids 11 (596 mg, 1.294 mmol) in toluene (6 ml), Et3N (0.36 ml,
2.58mmol, 2 equiv.), (PhO) 2P(O)N3 (0.33 ml, 1.53 mmol, 1.2 equiv.), and BnOH (0.27 ml, 2.61 mmol, 2 equiv.)
were added, and the mixture was stirred for 1 h at r.t., followed by refluxing for an additional 1 h. Toluene was
evaporated in vacuo, and the residue was dissolved in Et2O (30 ml) and 2m HCl (20 ml). The org. phase was
separated, washed with sat. NaHCO3, dried (MgSO4), and concentrated in vacuo to yield 860 mg of yellow oil.