Toluene → Benzhydrylidene-(3-(4-dimethylamino-cyclohex-1-enyl)-2-fluoro-phenyl)-amine

HRID 970730Notes

Reaction equation

HRID 970730 reaction equation
Br[C:2]1[C:3]([F:17])=[C:4]([C:8]2[CH2:13][CH2:12][CH:11]([N:14]([CH3:16])[CH3:15])[CH2:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:18](=[NH:31])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>CO.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].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>[C:18](=[N:31][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[CH2:13][CH2:12][CH:11]([N:14]([CH3:16])[CH3:15])[CH2:10][CH:9]=2)[C:3]=1[F:17])([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 58852349(4-(3-Bromo-2-fluoro-phenyl)-cyclohex-3-enyl)-dimethyl-amine

Product 1

HCID 86611762Benzhydrylidene-(3-(4-dimethylamino-cyclohex-1-enyl)-2-fluoro-phenyl)-amineYield 87.7%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolvent

Procedure

Combine (4-(3-bromo-2-fluoro-phenyl)-cyclohex-3-enyl)-dimethyl-amine (preparation 7, 1.70 g, 6.84 mmol), benzophenone imine (1.24 g, 6.84 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.104 g, 0.11 mmol), racemic BINAP (0.142 g, 0.228 mmol), and sodium t-butoxide (0.767 g, 0.8 mmol) with toluene (5 mL) and heat at reflux for 2 hr. Dissolve the reaction mixture in MeOH and filter through a SCX column (Bond Elut™, 10 g), wash with MeOH, elute the product with 2M NH3 in MeOH, evaporate the solvent, and further purify on a silica gel column (DCM:2M NH3 in MeOH, gradient) to give pure benzhydrylidene-(3-(4-dimethylamino-cyclohex-1-enyl)-2-fluoro-phenyl)-amine (2.39 g): MS (ES): m/z=399 (M+H)+. 1H NMR (CDCl3): δ 7.76 (m, 2H), 7.46 (m, 1H), 7.40 (m, 2H), 7.25 (m, 4H), 7.13 (m, 2H), 6.85 (m, 1H), 6.73 (m, 1H), 6.65 (m, 1H), 5.70 (m, 1H), 3.05 (m, 1H), 2.61 (s, 6H), 2.6-2.2 (m, 5H), 1.75 (m, 1H).

Workup

  1. temperatureat reflux for 2 hr
  2. filtrationfilter through a SCX column (Bond Elut™, 10 g)
  3. washwash with MeOH
  4. washelute the product with 2M NH3 in MeOH
  5. customevaporate the solvent
  6. customfurther purify on a silica gel column (DCM:2M NH3 in MeOH, gradient)

Sources & evidence

ORD record
ord-ada67f8b45354bccab32c3b06bf5d4ea
Source dataset
uspto-grants-2007_12
Patent number
US07312236B2

Reaction notes

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