Isopropanol → tert-Butyl (4-{(1R)-1-(4-fluoroanilino)-2-[(4-methoxybenzyl)thio]-3-oxo-3-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]propyl}phenoxy)acetate

HRID 254111ノート

反応式

HRID 254111 の反応式
[CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][S:8][CH2:9][C:10]([N:12]2[C@@H:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:15][O:14][C:13]2=[O:23])=[O:11])=[CH:5][CH:4]=1.[F:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]=[CH:34][C:35]2[CH:49]=[CH:48][C:38]([O:39][CH2:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[CH:37][CH:36]=2)=[CH:29][CH:28]=1.C(N(C(C)C)C(C)C)C.C(O)(C)C>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4].O>[F:26][C:27]1[CH:28]=[CH:29][C:30]([NH:33][C@H:34]([C:35]2[CH:49]=[CH:48][C:38]([O:39][CH2:40][C:41]([O:43][C:44]([CH3:46])([CH3:47])[CH3:45])=[O:42])=[CH:37][CH:36]=2)[CH:9]([S:8][CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:25][CH:24]=2)[C:10](=[O:11])[N:12]2[C@@H:16]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:15][O:14][C:13]2=[O:23])=[CH:31][CH:32]=1

参加物

9

反応物 4

HCID 3776IsopropanolHCID 81531DiisopropylethylamineHCID 59326632(4S)-3-{[(4-Methoxybenzyl)thio]acetyl}-4-phenyl-1,3-oxazolidin-2-oneHCID 86619087Tert-butyl (4-{[(4-fluorophenyl)imino]methyl}phenoxy)acetate

生成物 1

HCID 86619099tert-Butyl (4-{(1R)-1-(4-fluoroanilino)-2-[(4-methoxybenzyl)thio]-3-oxo-3-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]propyl}phenoxy)acetate収率 26%

試薬・触媒・溶媒 4

HCID 11026Titanium isopropoxide触媒HCID 24193Titanium Tetrachloride触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒3 回

実験手順

TiCl4 (1M in DCM, 7.2 ml, 7.2 mmol) was added to a solution of tetraisopropyl orthotitanate (0.71 ml 2.4 mmol) in DCM (40 ml) held at 0° C. under inert atmosphere. The mixture was stirred for 15 minutes, then (4S)-3-{[(4-methoxybenzyl)thio]acetyl}-4-phenyl-1,3-oxazolidin-2-one (3.4 g, 9.6 mmol) in dry DCM (20 ml) was added and the mixture was stirred for five minutes. Then tert-butyl (4-{[(4-fluorophenyl)imino]methyl}phenoxy)acetate (6.3 g, 19.0 mmol) in dry DCM (30 ml) was added and the mixture was given −40° C. and stirred for 20 minutes. Ethyl diisopropyl amine (3.3 ml, 19.0 mmol) was added and the mixture was stirred at −40° C. for 19 hours. The mixture was then given −78° C., added isopropanol (50 ml) and slowly given room temperature over night. Water (100 ml) was added and the mixture was stirred for 35 minutes at room temperature and then extracted twice with diethyl ether. The combined organic layer was washed with water, dried (MgSO4) and concentrated under reduced pressure. The crude product was dissolved in methanol and an off-white precipitate formed. Filtration and drying afforded 1.7 g (26%) of the title compound as an off-white solid. NMR (200 MHz): 1.5 (s, 9H), 3.65 (s, 1H), 3.8 (s, 3H), 4.1 (m, 1H), 4.4-4.6 (m, 4H), 5.0-5.2 (m, 2H), 5.4 (m, 1H), 6.4-6.6 (m, 2H), 6.7-7-4 (m, 15H).

後処理

  1. customheld at 0° C. under inert atmosphere
  2. stirringthe mixture was stirred for five minutes
  3. customwas given −40° C.
  4. stirringstirred for 20 minutes
  5. stirringthe mixture was stirred at −40° C. for 19 hours
  6. customwas then given −78° C.
  7. stirringthe mixture was stirred for 35 minutes at room temperature
  8. extractionextracted twice with diethyl ether
  9. washThe combined organic layer was washed with water
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe crude product was dissolved in methanol
  13. customan off-white precipitate formed
  14. filtrationFiltration
  15. customdrying

出典と根拠

ORDレコード
ord-ee3341b7268c424981be01b6069ee950
出典データセット
uspto-grants-2011_01
特許番号
US07871998B2

反応ノート

読み込み中…