2,3-Dihydroxybutanedioic Acid → 3-[2-[(4-Bromophenyl)-(4-fluorophenylamino)methyl]-5-(tert-butyl-dimethylsilanyloxy)-5-(4-fluorophenyl)pentanoyl]-4-phenyloxazolidin-2-one

HRID 2243621Notes

Reaction equation

HRID 2243621 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].[Br:34][C:35]1[CH:49]=[CH:48][C:38]([CH:39]=[N:40][C:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=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>[Br:34][C:35]1[CH:36]=[CH:37][C:38]([CH:39]([NH:40][C:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=2)[CH:12]([CH2:11][CH2:10][CH:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2])[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[C:13]([N:15]2[CH:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:18][O:17][C:16]2=[O:26])=[O:14])=[CH:48][CH:49]=1

Participants

10

Reactant 6

HCID 8752,3-Dihydroxybutanedioic AcidHCID 6397ChlorotrimethylsilaneHCID 81531DiisopropylethylamineHCID 904271N-[(4-Bromophenyl)methylene]-4-fluorobenzenamineHCID 121116183-[5-(tert-Butyldimethylsilanyloxy)-5-(4-fluorophenyl)pentanoyl]4-phenyloxazolidin-2-oneHCID 23665763Sodium Bisulfite

Product 1

HCID 222520673-[2-[(4-Bromophenyl)-(4-fluorophenylamino)methyl]-5-(tert-butyl-dimethylsilanyloxy)-5-(4-fluorophenyl)pentanoyl]-4-phenyloxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

4.4 g of 3-[5-(tert-butyldimethylsilanyloxy)-5-(4-fluorophenyl)pentanoyl]-4-phenyloxazolidin-2-one are dissolved in 40 ml of absolute dichloromethane. 5.2 g of (4-bromobenzylidene)-(4-fluorophenyl)amine and 8.6 ml of ethyldiisopropylamine are added, and the solution is then cooled to −10° C. 2.94 ml of trimethylsilyl chloride are then added dropwise, and during the addition, the temperature of the reaction mixture is maintained below −5° C. The reaction solution is then stirred at −10° C. for half an hour and then cooled to −30° C., and 1.2 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, 10 ml of glacial acetic acid, 100 ml of 7% strength aqueous tartaric acid solution and finally 100 ml of 20% strength aqueous sodium hydrogensulfite solution are added with stirring. The mixture is then extracted twice 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. C39H43BrF2N2O4Si (749) MS (ESI): M+

Workup

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

Sources & evidence

ORD record
ord-67a0a9ffe74d4d9daeb2304296e3b25c
Source dataset
uspto-grants-2010_03
Patent number
US07674773B2

Reaction notes

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