1,2-Dimethoxyethane → HCID 178500093, compound

HRID 2389125Notes

Reaction equation

HRID 2389125 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([C:12]([F:15])([F:14])[F:13])=[C:7]([O:16][C@H:17]1[CH2:22][CH2:21][C@H:20]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:19][CH2:18]1)[CH:6]=[CH:5]2.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].COCCOC.[CH3:61][O:62][C:63](=[O:70])[CH2:64][CH2:65][CH2:66][N+:67]([O-:69])=[O:68]>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]>[C:23]([C@H:20]1[CH2:21][CH2:22][C@H:17]([O:16][C:7]2[C:8]([C:12]([F:13])([F:14])[F:15])=[C:9]3[C:4](=[CH:5][CH:6]=2)[CH:3]=[C:2]([CH:66]([N+:67]([O-:69])=[O:68])[CH2:65][CH2:64][C:63]([O:62][CH3:61])=[O:70])[CH:11]=[CH:10]3)[CH2:18][CH2:19]1)([CH3:26])([CH3:24])[CH3:25]

Participants

7

Reactant 5

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 25604Methyl 4-nitrobutyrateHCID 27349372-(Di-tert-butylphosphino)-2'-methyl-1,1'-biphenylHCID 178445719HCID 178445719, compound

Product 1

HCID 178500093HCID 178500093, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A 200 mL round-bottom flask containing a stir bar was charged with 6-bromo-2-(trans-4-tert-butylcyclohexyloxy)-1-(trifluoromethyl)naphthalene (5.00 g, 11.6 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.400 g, 0.437 mmol; Strem), 2-(di-t-butylphosphino)-2′-methylbiphenyl (0.546 g, 1.75 mmol; Strem), and cesium carbonate (4.55 g, 14.0 mmol; Alfa Aesar). The reaction vessel was capped with a rubber septum, evacuated, backfilled with argon three times and 1,2-dimethoxyethane (100 mL, 1000 mmol) and 4-nitro-butyric acid methyl ester (3.02 mL, 24.4 mmol) were added via syringe under argon. After the mixture was stirred vigorously for 2 min at room temperature, the flask was equipped with a condensor and heated at 50° C. overnight. The reaction was allowed to cool to ambient temperature and quenched with a solution of sat. aqueous ammonium chloride. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phase was washed with water then dried with magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was dissolved in methylene chloride and absorbed onto silica gel, then purified by flash column chromatography (0-20% hexanes in ethylacetate) to give 2.34 g of the title compound in 41% yield.

Workup

  1. additionA 200 mL round-bottom flask containing a stir bar
  2. customThe reaction vessel was capped with a rubber septum
  3. customevacuated
  4. additionwere added via syringe under argon
  5. customthe flask was equipped with a condensor
  6. temperatureheated at 50° C. overnight
  7. temperatureto cool to ambient temperature
  8. customquenched with a solution of sat. aqueous ammonium chloride
  9. customThe layers were separated
  10. extractionthe aqueous phase was extracted with ethyl acetate
  11. washThe combined organic phase was washed with water
  12. dry with materialthen dried with magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. dissolutionThe crude product was dissolved in methylene chloride
  16. customabsorbed onto silica gel
  17. custompurified by flash column chromatography (0-20% hexanes in ethylacetate)

Sources & evidence

ORD record
ord-53441223816e45c0a2b4fddc4b14f62e
Source dataset
uspto-grants-2012_09
Patent number
US08269043B2

Reaction notes

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