Benzophenone imine → HCID 58562976, compound

HRID 403238Notes

Reaction equation

HRID 403238 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([C@:8]2([CH3:18])[CH2:14][C:13]([CH3:16])([CH3:15])[O:12][CH2:11][C:10](=[O:17])[NH:9]2)[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:56](=[NH:69])([C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=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:56](=[N:69][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([C@:8]2([CH3:18])[CH2:14][C:13]([CH3:16])([CH3:15])[O:12][CH2:11][C:10](=[O:17])[NH:9]2)[CH:7]=1)([C:63]1[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=1)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=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 58563092HCID 58563092, compound

Product 1

HCID 58562976HCID 58562976, compoundYield 89%

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 (S)-5-(5-bromo-2-fluoro-phenyl)-5,7,7-trimethyl-[1,4]oxazepan-3-one (intermediate A16A) (1.0 g, 3.0 mmol) in toluene (20 ml), sodium tert-butoxide (NaOBut) (865 mg, 9.0 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (t-Bu X-phos) (127 mg, 10 mol %) and tris(dibenzylideneacetone)dipalladium chloroform complex (Pd2(dba)3.CHCl3) (93 mg, 3 mol %) followed by benzophenone imine (1.07 mL, 6.0 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 sulphate. 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 (S)-5-[5-(benzhydrylidene-amino)-2-fluoro-phenyl]-5,7,7-trimethyl-[1,4]oxazepan-3-one (1.15 g, 88%) as light yellow foam. MS (ISP): m/z=431.3 [(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 sulphate
  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-9262f89de9b947adb30f4971271911cb
Source dataset
uspto-grants-2014_06
Patent number
US08748418B2

Reaction notes

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