Benzophenone imine → HCID 76831142, compound

HRID 1186170Notes

Reaction equation

HRID 1186170 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:17])=[C:6]([C:8]23[CH2:15][CH:14]2[CH2:13][O:12][CH2:11][C:10](=[O:16])[NH:9]3)[CH:7]=1.CC(C)([O-])C.[Na+].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:54](=[NH:67])([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(Cl)(Cl)Cl.O>[C:54](=[N:67][C:2]1[CH:3]=[CH:4][C:5]([F:17])=[C:6]([C:8]23[CH2:15][CH:14]2[CH2:13][O:12][CH2:11][C:10](=[O:16])[NH:9]3)[CH:7]=1)([C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1

Participants

8

Reactant 4

HCID 136809Benzophenone imineHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxideHCID 76831082HCID 76831082, compound

Product 1

HCID 76831142HCID 76831142, compoundYield 85.2%

Reagents, catalysts & solvents 3

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)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

Under argon in a sealed tube was added to a solution of (1SR,7RS)-1-(5-bromo-2-fluoro-phenyl)-5-oxa-2-aza-bicyclo[5.1.0]octan-3-one (intermediate B10A) (405 mg, 1.349 mmol) in toluene (9 ml), sodium tert-butoxide (NaOBut) (389 mg, 4.05 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (t-Bu X-phos) (57 mg, 10 mol %) and tris(dibenzylideneacetone)dipalladium chloroform complex (Pd2(dba)3.CHCl3)(42 mg, 3 mol %) followed by benzophenone imine (453 uL, 2.7 mmol). The tube was sealed under argon and the mixture was stirred at 105° C. for 18 h to 2.5 days. The mixture was cooled to 23° C., poured into water, extracted with ethyl acetate, and the organic layer was washed with brine and dried over sodium sulfate. Removal of the solvent in vacuum left a brown oil, which was purified by silica gel column chromatography with n-heptane/ethyl acetate to give the title compound as a yellow foam (460 mg, 85%). MS (ISP): m/z=401.3 [(M+H)+].

Workup

  1. customThe tube was sealed under argon
  2. temperatureThe mixture was cooled to 23° C.
  3. extractionextracted with ethyl acetate
  4. washthe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. customRemoval of the solvent in vacuum
  7. waitleft a brown oil, which
  8. customwas purified by silica gel column chromatography with n-heptane/ethyl acetate

Sources & evidence

ORD record
ord-5dc78d6f7ac3408b97893e0e058f76ae
Source dataset
uspto-grants-2014_03
Patent number
US08673894B2

Reaction notes

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