2,3-Dihydroxybutanedioic Acid → 3-[5-(tert-Butyldimethylsilanyloxy)-5-(4-fluorophenyl)-1-(4-fluorophenylamino)-2-(2-oxo-4-phenyloxazolidine-3-carbonyl)pentyl]benzonitrile

HRID 1725276Notes

Reaction equation

HRID 1725276 reaction equation
C(N(C(C)C)CC)(C)C.[Si:10]([O:17][CH:18]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)[CH2:19][CH2:20][CH2:21][C:22]([N:24]1[CH:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:27][O:26][C:25]1=[O:35])=[O:23])([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].[F:43][C:44]1[CH:49]=[CH:48][C:47]([N:50]=[CH:51][C:52]2[CH:53]=[C:54]([CH:57]=[CH:58][CH:59]=2)[C:55]#[N:56])=[CH:46][CH:45]=1.C[Si](Cl)(C)C.C(O)(=O)C(C(C(O)=O)O)O.S([O-])(O)=O.[Na+]>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl.C(O)(=O)C>[Si:10]([O:17][CH:18]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)[CH2:19][CH2:20][CH:21]([C:22]([N:24]1[CH:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:27][O:26][C:25]1=[O:35])=[O:23])[CH:51]([C:52]1[CH:53]=[C:54]([CH:57]=[CH:58][CH:59]=1)[C:55]#[N:56])[NH:50][C:47]1[CH:46]=[CH:45][C:44]([F:43])=[CH:49][CH:48]=1)([C:13]([CH3:16])([CH3:14])[CH3:15])([CH3:12])[CH3:11]

Participants

10

Reactant 6

HCID 8752,3-Dihydroxybutanedioic AcidHCID 6397ChlorotrimethylsilaneHCID 81531DiisopropylethylamineHCID 121116183-[5-(tert-Butyldimethylsilanyloxy)-5-(4-fluorophenyl)pentanoyl]4-phenyloxazolidin-2-oneHCID 222520513-[(4-Fluorophenylimino)methyl]benzonitrileHCID 23665763Sodium Bisulfite

Product 1

HCID 222520683-[5-(tert-Butyldimethylsilanyloxy)-5-(4-fluorophenyl)-1-(4-fluorophenylamino)-2-(2-oxo-4-phenyloxazolidine-3-carbonyl)pentyl]benzonitrile

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

At 10° C., 24 ml of diisopropylethylamine are added to 14 g of 3-[5-(tert-butyldimethyl-silanyloxy)-5-(4-fluorophenyl)pentanoyl]-4-phenyloxazolidin-2-one (10) and 12.5 g of 3-[(4-fluorophenylimino)methyl]benzonitrile 11 in 200 ml of methylene chloride, and 7.1 ml of trimethylsilyl chloride are added dropwise. After 1 h, 3.4 ml of titanium tetrachloride are added dropwise at −10° C. The mixture is stirred at −10° C. for 3 h and then allowed to stand at −30° C. for another 12 h. 8 ml of acetic acid and 140 ml of a 7% strength aqueous tartaric acid solution are then added, and stirring is continued at room temperature for another 2 h. 50 ml of 20% strength aqueous sodium hydrogen sulfite solution are added, and the mixture is then stirred for another hour and extracted with methylene chloride. The organic phase is dried over magnesium sulfate, concentrated and purified by silica gel chromatography (ethyl acetate/heptane=1/3->1/1). This gives 12

Workup

  1. additionare added dropwise
  2. waitto stand at −30° C. for another 12 h
  3. stirringstirring
  4. waitis continued at room temperature for another 2 h
  5. stirringthe mixture is then stirred for another hour
  6. extractionextracted with methylene chloride
  7. dry with materialThe organic phase is dried over magnesium sulfate
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography (ethyl acetate/heptane=1/3->1/1)

Sources & evidence

ORD record
ord-3e4d8c23deaa4cdc9f118fcf31fef7ab
Source dataset
uspto-grants-2009_02
Patent number
US07488829B2

Reaction notes

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