Hydrochloric Acid → HCID 67426573, compound

HRID 2200167Notes

Reaction equation

HRID 2200167 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6](=[O:12])[C:5]12[CH2:14][CH2:13]1.C(=[NH:28])(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].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.Cl>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].CCOC(C)=O.C1COCC1.O1CCOCC1>[NH2:28][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6](=[O:12])[C:5]12[CH2:14][CH2:13]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 71743936HCID 71743936, compound

Product 1

HCID 67426573HCID 67426573, compoundYield 93.3%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Add 5′-bromo-1′-methylspiro[cyclopropane-1,3′-indolin]-2′-one (1.0 g, 4.0 mmol), benzophenone imine (1.4 g, 8.0 mmol), cesium carbonate (3.2 g, 10.0 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (BINAP, 500 mg, 0.80 mmol), tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3, 500 mg, 0.55 mmol] to dioxane (20 mL), stir the reaction under nitrogen atmosphere at 110° C. overnight. Cool to room temperature; filter off the solid, concentrate the filtrate under reduced pressure to give a residue. Add hydrochloric acid (1N, 2 mL) and THF (15 mL) to the residue; stir the mixture for 30 mins at room temperature. TLC (PE:EtOAc=1:1) shows the reaction is almost complete. Concentrate the mixture under reduce pressure to give the crude product, purify by flash chromatography (silica gel, EtOAc:PE=1:1) to afford the title compound as a yellow solid (0.7 g, 93.3%). MS: (M+1): 189.1.

Workup

  1. customthe reaction under nitrogen atmosphere at 110° C. overnight
  2. filtrationfilter off the solid
  3. concentrationconcentrate the filtrate under reduced pressure
  4. customto give a residue
  5. stirringstir the mixture for 30 mins at room temperature
  6. concentrationConcentrate the mixture
  7. customto give the crude product
  8. custompurify by flash chromatography (silica gel, EtOAc:PE=1:1)

Sources & evidence

ORD record
ord-6485d68a4222400da8cc91d1e7f0daea
Source dataset
uspto-grants-2016_06
Patent number
US09359338B2

Reaction notes

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