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 1366314Notes

Reaction equation

HRID 1366314 reaction equation
[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:36]=[CH:37][C:38]([O:39][CH2:40][C:41]([O:43][C:44]([CH3:45])([CH3:46])[CH3:47])=[O:42])=[CH:48][CH:49]=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

Participants

9

Reactant 4

HCID 3776IsopropanolHCID 81531DiisopropylethylamineHCID 59326632(4S)-3-{[(4-Methoxybenzyl)thio]acetyl}-4-phenyl-1,3-oxazolidin-2-oneHCID 178451335HCID 178451335, compound

Product 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

Reagents, catalysts & solvents 4

HCID 11026Titanium isopropoxideCatalystHCID 24193Titanium TetrachlorideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent4×

Procedure

TiCl4 (1M in CH2Cl2, 12.6 mL, 12.6 mmol) was added to a solution of tetraisopropyl orthotitanate (1.24 mL, 4.2 mmol) in CH2Cl2 (80 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 (6.0 g, 16.8 mmol) in dry CH2Cl2 (60 mL) was added dropwise over 30 minutes and the mixture was stirred for ten minutes. Then tert-butyl (4-{(E)-[(4-fluorophenyl)imino]methyl}phenoxy)acetate (11.1 g, 33.6 mmol) in dry CH2Cl2 (60 mL) was added dropwise over 30 minutes, the mixture was given −40° C. and stirred for 20 minutes. Ethyl diisopropyl amine (5.8 mL, 33.6 mmol) in 20 mL CH2Cl2 was added dropwise over 20 minutes and the mixture was stirred at −40° C. for 90 minutes. The mixture was then given −78° C., added isopropanol (50 mL) and slowly given room temperature over two hours. H2O (100 mL) was added and the mixture was stirred for 20 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 a precipitate formed. Filtration and drying the title compound.

Workup

  1. customheld at 0° C. under inert atmosphere
  2. stirringthe mixture was stirred for ten minutes
  3. customwas given −40° C.
  4. stirringstirred for 20 minutes
  5. stirringthe mixture was stirred at −40° C. for 90 minutes
  6. customwas then given −78° C.
  7. stirringthe mixture was stirred for 20 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. customa precipitate formed
  14. filtrationFiltration
  15. dry with materialdrying the title compound

Sources & evidence

ORD record
ord-2bf9878c236e4236bedd4e596796b38e
Source dataset
uspto-grants-2011_02
Patent number
US07893048B2

Reaction notes

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