Toluene → HCID 66938556, compound

HRID 1716899Notes

Reaction equation

HRID 1716899 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12](Br)[CH:11]=2)[CH2:4][CH2:3]1.C(=[NH:31])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C(OCC)(=O)C.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].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([NH2:31])[CH:11]=2)[CH2:4][CH2:3]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 66938969HCID 66938969, compound

Product 1

HCID 66938556HCID 66938556, compoundYield 86%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Combine 1-methyl-4-(N-(3-bromo-5-fluorophenyl)methylamino)piperidine (Preparation 30, 2.90 g, 9.63 mmol), benzophenone imine (1.94 mL, 11.55 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.24 g, 0.39 mmol), sodium t-butoxide (1.26 g, 13.48 mmol), and toluene (60 mL), stir and heat to 80° C. After 10 minutes, add Pd2(dba)3 (0.17 g, 0.19 mmol). After 3 hr at 80° C., cool to ambient temperature. Dilute with ethyl acetate (100 mL) and wash with water (50 mL). Separate organic layer, dry over sodium sulfate, filter and concentrate. Dissolve this material in tetrahydrofuran (120 mL) and treat with 1M aqueous hydrochloric acid solution (40 mL). After stirring at ambient temperature for 1 hr, add 2M sodium hydroxide solution until basic (21 mL). Extract with ethyl acetate (2×100 mL). Wash organic layer with saturated aqueous NaCl solution (75 mL), dry over sodium sulfate, filter and concentrate to an oil. Purify residue by silica gel flash chromatography eluting with 10% (2M NH3 in methanol) in CH2Cl2 to obtain 1.96 g (86%) of the title compound.

Workup

  1. waitAfter 3 hr at 80° C.
  2. temperaturecool to ambient temperature
  3. washwash with water (50 mL)
  4. dry with materialSeparate organic layer, dry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. dissolutionDissolve this material in tetrahydrofuran (120 mL)
  8. additiontreat with 1M aqueous hydrochloric acid solution (40 mL)
  9. additionadd 2M sodium hydroxide solution until basic (21 mL)
  10. extractionExtract with ethyl acetate (2×100 mL)
  11. dry with materialWash organic layer with saturated aqueous NaCl solution (75 mL), dry over sodium sulfate
  12. filtrationfilter
  13. concentrationconcentrate to an oil
  14. washPurify residue by silica gel flash chromatography eluting with 10% (2M NH3 in methanol) in CH2Cl2

Sources & evidence

ORD record
ord-9e59f869bd1749da9d119ecc6c36d0dc
Source dataset
uspto-grants-2010_09
Patent number
US07803813B2

Reaction notes

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