1,2-Dibromoethane → HCID 66920480, compound

HRID 1510091Notes

Reaction equation

HRID 1510091 reaction equation
BrCCBr.[Cl:5][C:6]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:7]=1[CH2:8]Br.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:28]([C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:31]=2Cl)=[O:29])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN1C(=O)CCC1.[Zn].C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Ni+2]>[C:15]([O:19][C:20]([N:22]1[CH2:23][CH2:24][N:25]([C:28]([C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:31]=2[CH2:8][C:7]2[CH:10]=[C:11]([F:14])[CH:12]=[CH:13][C:6]=2[Cl:5])=[O:29])[CH2:26][CH2:27]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

9

Reactant 3

HCID 78391,2-DibromoethaneHCID 27736232-Chloro-5-fluorobenzyl bromideHCID 45257316HCID 45257316, compound

Product 1

HCID 66920480HCID 66920480, compoundYield 23.1%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 9834912Nickel(II) acetylacetonateCatalystHCID 8028TetrahydrofuranSolvent3×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of zinc (176 mg, 2.69 mmol) in dry THF (1 ml) in a dry flask under argon was added 1,2-dibromoethane (5.79 μl, 67.2 μmol). The mixture was heated three times to reflux with a heat-gun. After 5 min the flask was placed in an ice bath and a solution of 2-chloro-5-fluoro-benzylbromide (182 μl, 1.34 mmol) in dry THF (1.5 ml) was added slowly, so that the temperature remained at 0° C. The mixture was stirred at 0° C. for 3 h. Then the cooled suspension was added dropwise to a precooled solution (0° C.) of the compound of example 16, step 1 (59.0 mg, 134 μmol), nickel acetylacetonate (3.44 mg, 13.4 μmol) and tetrabutylammonium iodide (149 mg, 402 μmol) in THF (4 ml) and NMP (2 ml). The reaction mixture was stirred at 0° C. for 3 h and then at room temperature for 48 h. The mixture was quenched with water and extracted with EA. The organic layer was separated, dried over sodium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by preparative HPLC. The eluate was lyophilized overnight to give 17 mg of the title compound.

Workup

  1. temperatureThe mixture was heated three times
  2. temperatureto reflux with a heat-gun
  3. customremained at 0° C
  4. stirringThe reaction mixture was stirred at 0° C. for 3 h
  5. waitat room temperature for 48 h
  6. customThe mixture was quenched with water
  7. extractionextracted with EA
  8. customThe organic layer was separated
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customThe residue was purified by preparative HPLC
  13. waitThe eluate was lyophilized overnight

Sources & evidence

ORD record
ord-e3701d06c94c45bab2f5f48706514739
Source dataset
uspto-grants-2012_07
Patent number
US08211885B2

Reaction notes

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