Benzophenone imine → 6-Amino-1-isopropyl-4,4,7-trimethyl-2-oxo-1,2,3,4-tetrahydroquinoline

HRID 365518Notes

Reaction equation

HRID 365518 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[CH3:12])[N:8]([CH:13]([CH3:15])[CH3:14])[C:7](=[O:16])[CH2:6][C:5]2([CH3:18])[CH3:17].C(=[NH:32])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CCOCC.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]>[NH2:32][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[CH3:12])[N:8]([CH:13]([CH3:15])[CH3:14])[C:7](=[O:16])[CH2:6][C:5]2([CH3:18])[CH3:17]

Participants

8

Reactant 4

HCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 232919176-Bromo-1-isopropyl-4,4,7-trimethyl-2-oxo-1,2,3,4-tetrahydroquinoline2×HCID 23676156Sodium t-butoxide

Product 1

HCID 232919116-Amino-1-isopropyl-4,4,7-trimethyl-2-oxo-1,2,3,4-tetrahydroquinolineYield 56%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 6-bromo-1-isopropyl-4,4,7-trimethyl-2-oxo-1,2,3,4-tetrahydroquinoline (Compound 17, 2.86 g, 9.2 mmol), benzophenone imine (1.54 g, 8.5 mmol) in 25.0 mL of toluene was degassed with argon for 20 minutes. To this solution was added sodium t-butoxide (1.16 g, 1.2 mmol), tris(dibenzylideneacetone)dipalladium(0) (97 mg, 0.11 mmol) and BINAP (0.18 g, 0.29 mmol) consecutively. The reaction mixture was then heated at 80° C. for 24 hours. Thereafter it was cooled to room temperature, diluted with ether, filtered and concentrated. The residue was diluted with tetrahydrofuran (10.0 mL) and and 10% aqueous HCl and stirred for 1 hour. 0.5 M HCl and 30% hexane in ethyl acetate were then added. The layers were separated and the aqueous layer was made alkaline using saturated NaHCO3 and water. The aqueous layer was extracted with methylene chloride (2×). The combined organic extracts were washed with brine and dried (Na2SO4). The filtered solution was concentrated under reduced pressure and the crude product was purified by silica gel chromatography (30% ethyl acetate in hexanes) to give the title compound (0.63 g, 56%) as a solid.

Workup

  1. temperatureThereafter it was cooled to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated
  4. additionThe residue was diluted with tetrahydrofuran (10.0 mL) and and 10% aqueous HCl
  5. addition0.5 M HCl and 30% hexane in ethyl acetate were then added
  6. customThe layers were separated
  7. extractionThe aqueous layer was extracted with methylene chloride (2×)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationThe filtered solution was concentrated under reduced pressure
  11. customthe crude product was purified by silica gel chromatography (30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3cd63ecaf96f408980aa975e97253ee7
Source dataset
uspto-grants-2000_10
Patent number
US06127382

Reaction notes

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