Iodoethane → HCID 57785782, compound

HRID 1399238Notes

Reaction equation

HRID 1399238 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13]3=[N:14][C:15]4[C:20]([Cl:21])=[CH:19][CH:18]=[C:17]([CH:22]([O:27][CH:28]([F:30])[F:29])[C:23]([F:26])([F:25])[F:24])[C:16]=4[N:12]3[CH2:11][CH2:10][CH2:9]2)=[C:4]([CH3:31])[CH:3]=1.[OH-].[K+].C(P([C:64]([CH3:67])(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C(=O)([O-])[O-:69].[K+].[K+].ICC>COCCOC.[Cl-].[Na+].O.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].O>[Cl:21][C:20]1[C:15]2[N:14]=[C:13]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([O:69][CH2:64][CH3:67])=[CH:3][C:4]=4[CH3:31])[CH2:9][CH2:10][CH2:11][N:12]3[C:16]=2[C:17]([CH:22]([O:27][CH:28]([F:30])[F:29])[C:23]([F:26])([F:25])[F:24])=[CH:18][CH:19]=1

Participants

10

Reactant 5

HCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 57785911HCID 57785911, compound

Product 1

HCID 57785782HCID 57785782, compoundYield 80%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 57417360Sodium chloride; waterSolvent2×

Conditions

Temperature
100 °C

Procedure

Under nitrogen atmosphere, to a suspension of 1-(4-bromo-2-methylphenyl)-9-chloro-6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole (0.20 g, 0.38 mmol), potassium hydroxide (64.2 mg, 1.14 mmol), water (2 mL) and di-tert-butyl[3,4,5,6-tetramethyl-2′,4′,6′-tri(propan-2-yl)biphenyl-2-yl]phosphane (73.3 mg, 0.15 mmol) in 1,2-dimethoxyethane (2 mL) was added tris(dibenzylideneacetone)dipalladium(0) (34.9 mg, 0.04 mmol), and the mixture was stirred at 100° C. for 1 h. The reaction mixture was diluted with brine at room temperature, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with brine, and concentrated in vacuo. To a suspension of the residue in N,N-dimethylformamide (4 mL) was added potassium carbonate (35.5 mg, 0.26 mmol), and the mixture was stirred at room temperature for 5 min. To the reaction mixture was added iodoethane (0.02 mL, 0.26 mmol) at 0° C., and the mixture was stirred at room temperature for 87 h. The reaction mixture was diluted with brine, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 10-20% ethyl acetate/n-hexane gradient mixture. The desired fractions were concentrated in vacuo. The residual oil was crystallized from ethyl acetate/n-hexane to give the title compound as a colorless crystal (58.9 mg, 0.12 mmol, 32%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. concentrationconcentrated in vacuo
  4. additionTo a suspension of the residue in N,N-dimethylformamide (4 mL)
  5. stirringthe mixture was stirred at room temperature for 5 min
  6. stirringthe mixture was stirred at room temperature for 87 h
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe combined organic layer was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash column chromatography on silica gel eluting with a 10-20% ethyl acetate/n-hexane gradient mixture
  13. concentrationThe desired fractions were concentrated in vacuo
  14. customThe residual oil was crystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-ccfcb26b04ab413287bd3e27c0f926f3
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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