Binap, (A+-)- → 2-tert-butyl-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-(3-methoxyphenyl)-5-methyl-1,3-benzoxazole-4-carbonitrile

HRID 17282

Reaction equation

HRID 17282 reaction equation
C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Br[C:48]1[C:49]([C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([O:70][CH3:71])[CH:65]=2)=[C:50]([CH3:63])[C:51]([C:61]#[N:62])=[C:52]2[C:56]=1[O:55][C:54]([C:57]([CH3:60])([CH3:59])[CH3:58])=[N:53]2.[CH3:72][N:73]([CH3:79])[C@H:74]1[CH2:78][CH2:77][NH:76][CH2:75]1.CC(C)([O-])C.[Na+].O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:57]([C:54]1[O:55][C:56]2[C:52](=[C:51]([C:61]#[N:62])[C:50]([CH3:63])=[C:49]([C:64]3[CH:69]=[CH:68][CH:67]=[C:66]([O:70][CH3:71])[CH:65]=3)[C:48]=2[N:76]2[CH2:77][CH2:78][C@H:74]([N:73]([CH3:79])[CH3:72])[CH2:75]2)[N:53]=1)([CH3:60])([CH3:59])[CH3:58]

Participants

8

Reactant 5

HCID 634876Binap, (A+-)-HCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 23676156Sodium t-butoxideHCID 685848527-Bromo-2-tert-butyl-6-(3-methoxyphenyl)-5-methyl-1,3-benzoxazole-4-carbonitrileHCID 86585896Sodium bicarbonate water

Product 1

HCID 685853342-tert-butyl-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-(3-methoxyphenyl)-5-methyl-1,3-benzoxazole-4-carbonitrileYield 2.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Procedure

(R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (70.2 mg, 113 μmol) was dissolved in toluene (2.7 ml) under heat, cooled to room temperature, then palladium(II) acetate (16.9 mg, 75.1 μmol) was added followed by stirring for 1 minute. 7-Bromo-2-tert-butyl-6-(3-methoxyphenyl)-5-methyl-1,3-benzoxazole-4-carbonitrile (I-20) (300 mg, 751 μmol), (3S)-3-(dimethylamino)pyrrolidine (114 μl, 902 μmol), sodium tert-butoxide (101 mg, 1.05 mmol), toluene (2.7 ml) were successively put into it, followed by stirring at 80° C. for 16 hours. After cooling, saturated sodium bicarbonate water (50 ml) was added to the reaction liquid, the product was extracted with chloroform (50 ml×2). The organic layer was washed with saturated brine (50 ml), dried over anhydrous magnesium sulfate, concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=100:1), then further purified by silica gel thin-layer partitioning (chloroform:methanol:acetic acid=80:10:5) to obtain the entitled compound (7.3 mg, 2.2%) as a yellow semi-solid.

Workup

  1. temperatureunder heat
  2. stirringby stirring at 80° C. for 16 hours
  3. temperatureAfter cooling
  4. extractionthe product was extracted with chloroform (50 ml×2)
  5. washThe organic layer was washed with saturated brine (50 ml)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (chloroform:methanol=100:1)
  9. customfurther purified by silica gel thin-layer
  10. custompartitioning (chloroform:methanol:acetic acid=80:10:5)

Sources & evidence

ORD record
ord-f1cfd8a05f1c411688ae59ea86dccf30
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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