Benzophenone imine → HCID 66594463, compound

HRID 1091359Notes

Reaction equation

HRID 1091359 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C@@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[CH2:9]2)=[CH:4][CH:3]=1.C(=[NH:35])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+]>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.C(Cl)(Cl)Cl.[Pd].[Pd].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>[NH2:35][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C@@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[CH2:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 50992522(2S)-2-(4-bromophenyl)-4-[(1R)-1-phenylethyl]morpholine

Product 1

HCID 66594463HCID 66594463, compoundYield 96%

Reagents, catalysts & solvents 3

HCID 27342152-(Di-tert-butylphosphino)biphenylCatalystHCID 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 1140TolueneSolvent

Procedure

A solution of (2S)-2-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholine (15.6 g, 45 mmol), benzophenone imine (9 g, 50 mmol), tris(dibenzylideneacetone)-dipalladium(0)-chloroform adduct (0.93 g, 0.9 mmol), sodium tert-butoxide (6.0 g, 63 mmol) and 2-(di-t-butylphosphino)biphenyl (0.53 g, 1.8 mmol) in toluene (135 ml) was stirred at 95° C. for 4 hours. The solvent was removed in vacuo and the residue was partitioned between water and ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. To a solution of the resulting residue in tetrahydrofuran (180 ml) was added 6N hydrochloric acid (180 ml) and the mixture was stirred at room temperature for one hour. The solvent was removed in vacuo and the residue was partitioned between water and ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated. The resulting residue was purified by column chromatography on silica gel (hexane-AcOEt, 2:1) to give (2S)-2-(4-aminophenyl)-4-((1R)-1-phenylethyl)morpholine (12.2 g, 96%) as an oil.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between water and ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe solvent was removed under reduced pressure
  5. additionTo a solution of the resulting residue in tetrahydrofuran (180 ml) was added 6N hydrochloric acid (180 ml)
  6. customThe solvent was removed in vacuo
  7. customthe residue was partitioned between water and ethyl acetate
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. customthe solvent was evaporated
  10. customThe resulting residue was purified by column chromatography on silica gel (hexane-AcOEt, 2:1)

Sources & evidence

ORD record
ord-877e04a4b6354384ae3fcf5b978c7cf9
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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