2,3-Dihydroxybutanedioic Acid → 3-(5-(Tert-butyldimethylsilanyloxy)-5-(4-fluorophenyl)-2-[(4-fluorophenyl-amino)-(4-hydroxyphenyl)methyl]pentanoyl)-4-phenyloxazolidin-2-one

HRID 1612540Notes

Reaction equation

HRID 1612540 reaction equation
[Si:1]([O:8][CH:9]([C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)[CH2:10][CH2:11][CH2:12][C:13]([N:15]1[CH:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:18][O:17][C:16]1=[O:26])=[O:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]=[CH:42][C:43]2[CH:48]=[CH:47][C:46]([OH:49])=[CH:45][CH:44]=2)=[CH:37][CH:36]=1.C(N(C(C)C)C(C)C)C.C[Si](Cl)(C)C.C(O)(=O)C(C(C(O)=O)O)O.S([O-])(O)=O.[Na+]>ClCCl.[Ti](Cl)(Cl)(Cl)Cl.C(O)(=O)C>[Si:1]([O:8][CH:9]([C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)[CH2:10][CH2:11][CH:12]([CH:42]([NH:41][C:38]1[CH:39]=[CH:40][C:35]([F:34])=[CH:36][CH:37]=1)[C:43]1[CH:48]=[CH:47][C:46]([OH:49])=[CH:45][CH:44]=1)[C:13]([N:15]1[CH:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:18][O:17][C:16]1=[O:26])=[O:14])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

10

Reactant 6

HCID 8752,3-Dihydroxybutanedioic AcidHCID 6397ChlorotrimethylsilaneHCID 81531DiisopropylethylamineHCID 7202544-[[(4-Fluorophenyl)imino]methyl]phenolHCID 121116183-[5-(tert-Butyldimethylsilanyloxy)-5-(4-fluorophenyl)pentanoyl]4-phenyloxazolidin-2-oneHCID 23665763Sodium Bisulfite

Product 1

HCID 222520473-(5-(Tert-butyldimethylsilanyloxy)-5-(4-fluorophenyl)-2-[(4-fluorophenyl-amino)-(4-hydroxyphenyl)methyl]pentanoyl)-4-phenyloxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

10 g of 3-[5-(tert-butyldimethylsilanyloxy)-5-(4-fluorophenyl)pentanoyl]-4-phenyloxazolidin-2-one are dissolved in 80 ml of absolute dichlormethane. 9.12 g of 4-[(4-fluorophenylimino)methyl]phenol and 19.6 ml of ethyldiisopropylamine are added, and the solution is then cooled to −10° C. 6.7 ml of trimethylsilyl chloride are then added dropwise, the temperature of the reaction mixture being maintained at below −5° C. The reaction solution is stirred at −10° C. for half an hour and then cooled to −30° C., and 2.7 ml of titanium tetrachloride are added dropwise, the temperature being maintained between −30° C. and −15° C. This gives a black reaction solution which is stirred at −20° C. for another 3 h and then allowed to warm to 0° C. In the stated order, in intervals of 10 minutes, 6 ml of glacial acetic acid, 60 ml of 7% strength aqueous tartaric acid solution and finally 100 ml of 20% strength aqueous sodium hydrogensulfite solution are then added with stirring. The mixture is then extracted three times with dichloromethane and the organic phase is washed once with saturated sodium chloride solution and dried over sodium sulfate. The solvent is removed using a rotary evaporator and the residue is purified by column chromatography (SiO2; ethyl acetate/heptane 1:4). The product is obtained from diethyl ether/pentane as white crystals. C39H44F2N2O5Si (686) MS (ESI): M+−241

Workup

  1. temperaturethe temperature of the reaction mixture being maintained at below −5° C
  2. temperaturecooled to −30° C.
  3. temperaturethe temperature being maintained between −30° C. and −15° C
  4. customThis gives a black reaction solution which
  5. stirringis stirred at −20° C. for another 3 h
  6. temperatureto warm to 0° C
  7. stirringwith stirring
  8. extractionThe mixture is then extracted three times with dichloromethane
  9. washthe organic phase is washed once with saturated sodium chloride solution
  10. dry with materialdried over sodium sulfate
  11. customThe solvent is removed
  12. customa rotary evaporator
  13. customthe residue is purified by column chromatography (SiO2; ethyl acetate/heptane 1:4)
  14. customThe product is obtained from diethyl ether/pentane as white crystals

Sources & evidence

ORD record
ord-8394337632ce47b09d9191256cd019c1
Source dataset
uspto-grants-2006_01
Patent number
US06992067B2

Reaction notes

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