Toluene → HCID 86712807, compound

HRID 876373Notes

Reaction equation

HRID 876373 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[NH:10][C:11]2[O:12][CH2:13][CH2:14][C@:15]([C:20]3[CH:25]=[C:24](Br)[CH:23]=[CH:22][C:21]=3[F:27])([CH:17]([F:19])[F:18])[N:16]=2)=[CH:5][CH:4]=1.C1(C)C=CC=CC=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.[C:79](=[NH:92])([C:86]1[CH:91]=[CH:90][CH:89]=[CH:88][CH:87]=1)[C:80]1[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[NH:10][C:11]2[O:12][CH2:13][CH2:14][C@@:15]([CH:17]([F:19])[F:18])([C:20]3[CH:25]=[C:24]([N:92]=[C:79]([C:80]4[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=4)[C:86]4[CH:91]=[CH:90][CH:89]=[CH:88][CH:87]=4)[CH:23]=[CH:22][C:21]=3[F:27])[N:16]=2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 136809Benzophenone imineHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 71093128HCID 71093128, compound

Product 1

HCID 86712807HCID 86712807, compoundYield 62.4%

Reagents, catalysts & solvents 1

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)Catalyst

Conditions

Temperature
105 °C

Procedure

Under argon in a sealed tube were added to a solution of (S)—N-(bis(4-methoxyphenyl)(phenyl)methyl)-4-(5-bromo-2-fluorophenyl)-4-(difluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (intermediate E7.1) (725 mg, 1.16 mmol) in toluene (15 ml) sodium tert-butoxide (334 mg, 3.48 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (73.8 mg, 174 μmol) and tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (60.0 mg, 58.0 μmol) and benzophenone imine (420 mg, 389 μl, 2.32 mmol), the tube was sealed under argon and the mixture was stirred at 105° C. for 4 h. The brown solution was extracted with ethyl acetate/water. The organic layer was washed with brine, dried over Na2SO4, filtered and evaporated to give a brown oil. The residue was chromatographed on 20 g silica gel with ethyl acetate 0-50% to give (S)—N-(bis(4-methoxyphenyl)(phenyl)methyl)-4-(difluoromethyl)-4-(5-(diphenylmethyleneamino)-2-fluorophenyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (525 mg, 723 μmol, 62.4% yield) as a yellow oil. MS (ISP): m/z=726.8 [M+H]+.

Workup

  1. customthe tube was sealed under argon
  2. extractionThe brown solution was extracted with ethyl acetate/water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customto give a brown oil
  8. customThe residue was chromatographed on 20 g silica gel with ethyl acetate 0-50%

Sources & evidence

ORD record
ord-f5db0909be104a20a910f4a52840cc8d
Source dataset
uspto-grants-2015_03
Patent number
US08987255B2

Reaction notes

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