Benzophenone imine → HCID 57893589, compound

HRID 1822010Notes

Reaction equation

HRID 1822010 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17](Cl)[N:16]=2)[CH2:10][C:9]1([CH3:23])[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=[NH:37])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].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>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(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[N:16]=[C:17]([NH2:37])[CH:18]=[CH:19][CH:20]=2)[CH2:10][C:9]1([CH3:23])[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 57893742HCID 57893742, compound

Product 1

HCID 57893589HCID 57893589, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Combine 2-(1-benzyl-2,2-dimethyl-piperidin-4-yloxy)-6-chloro-pyridine (preparation 54, 0.57 g, 1.72 mmol), benzhydrylideneamine (0.31 g, 1.72 mmol) and toluene (20 mL), add sodium-t-butoxide (0.22 g, 2.24 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.043 g, 0.69 mmol), stir and heat at 80° C. After 10 min., add tris(dibenzylideneacetone)-dipalladium(0) (0.032 g, 0.345 mmol), stir and heat at 80° C. After 16 hr., add tris(dibenzylideneacetone)-dipalladium(0) (0.032 g, 0.345 mmol) and continue heating. After additional 24 hr., cool to ambient temperature. Partition between water (50 mL) and ethyl acetate (50 mL). Separate the organic layer, wash with aqueous NaCl solution (50 mL), dry over sodium sulfate, filter and concentrate. Dissolve residue in tetrahydrofuran (80 mL) and treat with 1M aqueous hydrochloric acid (30 mL) with stirring. After 1 hr., make the reaction mixture basic by adding 2M aqueous sodium hydroxide solution; extract with ethyl acetate. Separate the organic layer, dry over sodium sulfate, filter and concentrate. Purify residue by silica gel flash chromatography eluting with 5% (2M ammonia/methanol)/dichloromethane to of impure title compound (0.50 g). Mass spectrum (electrospray): m/z=312.2 (M+1).

Workup

  1. stirringstir
  2. temperatureheat at 80° C
  3. waitAfter 16 hr
  4. temperaturecontinue heating
  5. waitAfter additional 24 hr
  6. temperature, cool to ambient temperature
  7. customPartition between water (50 mL) and ethyl acetate (50 mL)
  8. customSeparate the organic layer
  9. washwash with aqueous NaCl solution (50 mL)
  10. dry with materialdry over sodium sulfate
  11. filtrationfilter
  12. concentrationconcentrate
  13. additionDissolve residue in tetrahydrofuran (80 mL) and treat with 1M aqueous hydrochloric acid (30 mL)
  14. stirringwith stirring
  15. waitAfter 1 hr
  16. additionby adding 2M aqueous sodium hydroxide solution
  17. extractionextract with ethyl acetate
  18. customSeparate the organic layer
  19. dry with materialdry over sodium sulfate
  20. filtrationfilter
  21. concentrationconcentrate
  22. washPurify residue by silica gel flash chromatography eluting with 5% (2M ammonia/methanol)/dichloromethane to of impure title compound (0.50 g)

Sources & evidence

ORD record
ord-01760da3a62e4521b85706e2ee263d5a
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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