1,2-Dibromoethane → HCID 66920426, compound

HRID 1510082Notes

Reaction equation

HRID 1510082 reaction equation
BrCCBr.[F:5][C:6]1[C:7]([CH3:14])=[C:8]([CH:11]=[CH:12][CH:13]=1)[CH2:9]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]=[C:36]([O:39][CH3:40])[CH:37]=3)[N:32]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:31]=2Cl)=[O:29])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1COCC1.[Zn].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[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]=[C:36]([O:39][CH3:40])[CH:37]=3)[N:32]([C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:31]=2[CH2:9][C:8]2[CH:11]=[CH:12][CH:13]=[C:6]([F:5])[C:7]=2[CH3:14])=[O:29])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

9

Reactant 4

HCID 78391,2-DibromoethaneHCID 27792443-Fluoro-2-methylbenzyl bromideHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 66920249HCID 66920249, compound

Product 1

HCID 66920426HCID 66920426, compoundYield 52.7%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of zinc (322 mg, 4.92 mmol) in dry THF (770 μl) in a dry flask under argon was added 1,2-dibromoethane (10.6 μl, 0.123 mmol). 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 3-fluoro-2-methyl-benzylbromide (500 mg, 2.46 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. The cooled suspension was added dropwise to a precooled solution (−78° C.) of B-OM-9-BBN (2.45 ml, 2.45 mmol, 1 M in hexane). The mixture was then stirred at room temperature for 30 min. DMF (7 ml) was added, followed by the compound of step 5 (115 mg, 245 μmol), palladium(II) acetate (5.49 mg, 24.5 μmol) and S—PHOS (20.1 mg, 48.9 μmol). The reaction mixture was stirred at 100° C. for 2 h. The cooled 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 72 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 mixture was then stirred at room temperature for 30 min
  5. stirringThe reaction mixture was stirred at 100° C. for 2 h
  6. customThe cooled 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-83f15201a9c143498f83c2c84e50f1b5
Source dataset
uspto-grants-2012_07
Patent number
US08211885B2

Reaction notes

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