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 254111Notes

Reaction equation

HRID 254111 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: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

Participants

9

Reactant 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

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)acetateYield 26%

Reagents, catalysts & solvents 4

HCID 11026Titanium isopropoxideCatalystHCID 24193Titanium TetrachlorideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-ee3341b7268c424981be01b6069ee950
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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