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

HRID 17270

Reaction equation

HRID 17270 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[O:65][CH:66]=[CH:67][CH:68]=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.[CH3:69][N:70]([CH3:76])[C@H:71]1[CH2:75][CH2:74][NH:73][CH2:72]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.[Cl-].[Na+].O.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[O:65][CH:66]=[CH:67][CH:68]=3)[C:48]=2[N:73]2[CH2:74][CH2:75][C@H:71]([N:70]([CH3:76])[CH3:69])[CH2:72]2)[N:53]=1)([CH3:60])([CH3:59])[CH3:58]

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 23676156Sodium t-butoxideHCID 685843857-Bromo-2-tert-butyl-6-(2-furyl)-5-methyl-1,3-benzoxazole-4-carbonitrile

Product 1

HCID 685851902-tert-Butyl-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-(2-furyl)-5-methyl-1,3-benzoxazole-4-CarbonitrileYield 13.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

(R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (10.4 mg, 16.7 μmol) was dissolved in toluene (0.5 ml) under heat, cooled to room temperature, palladium(II) acetate (2.5 mg, 11.1 μmol) was added, followed by stirring for 1 minute. This was put into a toluene (0.5 ml) suspension of 7-bromo-2-tert-butyl-6-(2-furyl)-5-methyl-1,3-benzoxazole-4-carbonitrile (I-10) (40 mg, 111 μmol), (3S)-3-(dimethylamino)pyrrolidine (16.9 μl, 134 μmol), sodium tert-butoxide (15.0 mg, 156 μmol), followed by stirring at 80° C. for 17 hours. After cooling, brine (30 ml) was added to the reaction liquid, the product was extracted with chloroform (30 ml×3). The organic layer was washed with saturated brine (30 ml), then dried over anhydrous magnesium sulfate, concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=1:0→100:1) to obtain the entitled compound (5.9 mg, 13%) as a yellow solid.

Workup

  1. temperatureunder heat
  2. stirringby stirring at 80° C. for 17 hours
  3. temperatureAfter cooling
  4. extractionthe product was extracted with chloroform (30 ml×3)
  5. washThe organic layer was washed with saturated brine (30 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=1:0→100:1)

Sources & evidence

ORD record
ord-b73f497e241d4b91b14e1eb6dea555b1
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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