1,2-Dimethoxyethane → 5-(3-Fluoro-4-nitrophenyl)-6-(4-fluorophenyl)-imidazo[2,1-b]oxazole

HRID 1711774Notes

Reaction equation

HRID 1711774 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[N:14]([C:15]=2I)[CH:13]=[CH:12][O:11]3)=[CH:4][CH:3]=1.[F:17][C:18]1[CH:19]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:21]=[CH:22][C:23]=1[N+:24]([O-:26])=[O:25].C([O-])([O-])=O.[Cs+].[Cs+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:17][C:18]1[CH:19]=[C:20]([C:15]2[N:14]3[C:10]([O:11][CH:12]=[CH:13]3)=[N:9][C:8]=2[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH:21]=[CH:22][C:23]=1[N+:24]([O-:26])=[O:25]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 467395312-(3-Fluoro-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 594578256-(4-Fluorophenyl)-5-iodo-imidazo[2,1-b]oxazole

Product 1

HCID 594578275-(3-Fluoro-4-nitrophenyl)-6-(4-fluorophenyl)-imidazo[2,1-b]oxazoleYield 83.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-(4-fluorophenyl)-5-iodo-imidazo[2,1-b]oxazole (10.0 g, 27.4 mmol; Preparation #A.1), 2-(3-fluoro-4-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (11.9 g, 41.1 mmol; Preparation #B.1), Cs2CO3 (28.6 g, 87.8 mmol), tetrakis(triphenylphosphine)palladium(0) (3.17 g, 2.74 mmol; Strem), DME (150 mL) and water (30.0 mL) was added to a flask with screw-thread top. The flask was sealed and heated at about 100° C. for about 16 h. After cooling to ambient temperature the reaction was concentrated under reduced pressure to remove organic solvent. The resulting mixture was diluted with water (200 mL) and EtOAc (200 mL) then filtered to remove insoluble material. The layers were separated and the aqueous layer was extracted with additional EtOAc (2×200 mL). The combined organic layers were washed with brine, dried over Na2SO4, decanted, and concentrated. The crude material was purified by silica gel chromatography using DCM to give the title compound (7.80 g, 78%): LC/MS (Table 1, Method b) Rt=2.19 min; MS m/z: 342.1 (M+H)+.

Workup

  1. additionwas added to a flask with screw-thread top
  2. customThe flask was sealed
  3. temperatureAfter cooling to ambient temperature the reaction
  4. concentrationwas concentrated under reduced pressure
  5. customto remove organic solvent
  6. additionThe resulting mixture was diluted with water (200 mL) and EtOAc (200 mL)
  7. filtrationthen filtered
  8. customto remove insoluble material
  9. customThe layers were separated
  10. extractionthe aqueous layer was extracted with additional EtOAc (2×200 mL)
  11. washThe combined organic layers were washed with brine
  12. dry with materialdried over Na2SO4
  13. customdecanted
  14. concentrationconcentrated
  15. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-5da84b78aacf4498965b7dde6e009fe2
Source dataset
uspto-grants-2010_09
Patent number
US07790741B2

Reaction notes

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