Acetic Acid → {1-(4-Fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl}-benzonitrile

HRID 2243597Notes

Reaction equation

HRID 2243597 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:43])[CH2:9][CH2:10][CH:11]([C:29](N2C(C3C=CC=CC=3)COC2=O)=[O:30])[CH:12]([C:21]2[CH:28]=[CH:27][C:24](C#N)=[CH:23][CH:22]=2)[NH:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.O.O.O.[F-].[CH2:48]([N+:52](CCCC)(CCCC)CCCC)CCC.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.C(O)(=O)C>C(OC)(C)(C)C>[F:20][C:17]1[CH:18]=[CH:19][C:14]([N:13]2[C:29](=[O:30])[CH:11]([CH2:10][CH2:9][CH:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[OH:43])[CH:12]2[C:21]2[CH:28]=[CH:27][CH:24]=[CH:23][C:22]=2[C:48]#[N:52])=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 11708267BistrimethylsilylacetamidHCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 222520644-[5-(4-Fluorophenyl)-1-(4-fluorophenylamino)-5-hydroxy-2-(2-oxo-4-phenyloxazolidine-3-carbonyl)-pentyl]-benzonitrile

Product 1

HCID 22252073{1-(4-Fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl}-benzonitrile

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
40 °C

Procedure

2 g of 5 are dissolved in 20 ml of methyl tert-butyl ether and, with 100 mg of tetrabutylammonium fluoride trihydrate and 1.3 ml of bistrimethylsilylacetamide, heated at 40° C. for about 1 h. The reaction is monitored by thin-layer chromatography. After the reaction has ended, initially 0.2 ml of glacial acetic acid is added, and the mixture is stirred for 30 min and concentrated. The residue is treated with 20 ml of a mixture of isopropanol/2N sulfuric acid=10:1 and stirred for 1 hour. Following the addition of a spatula tip of solid sodium bicarbonate, the mixture is once more concentrated under reduced pressure, the residue is taken up in ethyl acetate, the org. phase is washed with water and dried and the residue is, after removal of the solvent, purified by column chromatography (SiO2, CH2Cl2/methanol=100:1). This gives 6 of molecular weight 418.45 (C25H20F2N2O2); MS (DCI+): 419 (M+H+).

Workup

  1. concentrationconcentrated
  2. additionThe residue is treated with 20 ml of a mixture of isopropanol/2N sulfuric acid=10:1
  3. stirringstirred for 1 hour
  4. additionthe addition of a spatula tip of solid sodium bicarbonate
  5. concentrationthe mixture is once more concentrated under reduced pressure
  6. washphase is washed with water
  7. customdried
  8. customafter removal of the solvent
  9. custompurified by column chromatography (SiO2, CH2Cl2/methanol=100:1)
  10. customThis gives 6 of molecular weight 418.45 (C25H20F2N2O2)

Sources & evidence

ORD record
ord-60238ad9df004e39ad5cce3fdb954cb1
Source dataset
uspto-grants-2010_03
Patent number
US07674773B2

Reaction notes

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