Benzophenone imine → HCID 57893613, compound

HRID 1821998Notes

Reaction equation

HRID 1821998 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=2)[CH2:10][C@@H:9]1[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=[NH:36])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].C([O-])(=O)C.[Na+].Cl.NO>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].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.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH2:36])[CH:16]=2)[CH2:10][C@@H:9]1[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

10

Reactant 5

HCID 136809Benzophenone imineHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 23676156Sodium t-butoxideHCID 57893679HCID 57893679, compound

Product 1

HCID 57893613HCID 57893613, compoundYield 59%

Reagents, catalysts & solvents 4

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Combine 4-(3-bromo-phenoxy)-cis 2-methyl-piperidine-1-carboxylic acid tert-butyl ester isomer 1 (preparation 22, 2.47 g, 6.67 mmol), benzhydrylideneamine (1.45 g, 8.0 mmol), toluene (100 mL), sodium-t-butoxide (0.9 g, 9.34 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.17 g, 0.27 mmol), stir and heat at 100° C. After 10 min., add tris(dibenzylideneacetone)-dipalladium(0) (0.12 g, 0.13 mmol), stir and heat at 100° C. After 4 hr., cool to ambient temperature and partition between water (200 mL) and 4:1 hexane:ethyl acetate (200 mL). Separate organic layer, wash with water (100 mL) and aqueous NaCl solution (100 mL). Dry organic layer over sodium sulfate, filter and concentrate to an oil. Dissolve residue in methanol (80 mL) and treat with sodium acetate (1.31 g, 16.01 mmol) followed by hydroxylamine monohydrogen chloride (0.83 g, 12.0 mmol) with stirring. After 1 hr., partition between 4:1 hexane:ethyl acetate (200 mL) and 0.5 M aqueous sodium hydroxide solution (200 mL). Separate organic layer, wash with aqueous NaCl solution (100 mL), dry over sodium sulfate, filter and concentrate. Purify residue by silica gel flash chromatography eluting with 4:1 hexanes:ethyl acetate to obtain the title compound (1.17 g, 59%). 1H NMR (CDCl3): 7.05 (m, 1H), 6.3 (m, 2H), 6.25 (m, 1H), 4.6 (m, 1H), 4.35 (m, 1H), 3.85 (m, 1H), 3.7 (bs, 2H), 3.25 (m, 1H), 1.95 (m, 2H), 1.8 (m, 1H), 1.7 (m, 1H), 1.45 (s, 9H), 1.3 (d, 3H).

Workup

  1. stirringstir
  2. temperatureheat at 100° C
  3. waitAfter 4 hr
  4. temperature, cool to ambient temperature
  5. custompartition between water (200 mL) and 4:1 hexane
  6. washSeparate organic layer, wash with water (100 mL) and aqueous NaCl solution (100 mL)
  7. filtrationDry organic layer over sodium sulfate, filter
  8. concentrationconcentrate to an oil
  9. stirringwith stirring
  10. waitAfter 1 hr
  11. custom, partition between 4:1 hexane
  12. washSeparate organic layer, wash with aqueous NaCl solution (100 mL)
  13. dry with materialdry over sodium sulfate
  14. filtrationfilter
  15. concentrationconcentrate
  16. washPurify residue by silica gel flash chromatography eluting with 4:1 hexanes

Sources & evidence

ORD record
ord-817ee08185a7435f9b08710e71154216
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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