2-Chloro-6-fluorobenzyl bromide → HCID 66920546, compound

HRID 1510089Notes

Reaction equation

HRID 1510089 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:17]=2Cl)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[Cl:37][C:38]1[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:39]=1[CH2:40]Br>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:17]=2[CH2:40][C:39]2[C:42]([F:46])=[CH:43][CH:44]=[CH:45][C:38]=2[Cl:37])=[O:15])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 27736252-Chloro-6-fluorobenzyl bromideHCID 45257316HCID 45257316, compoundHCID 178418339Butyllithium

Product 1

HCID 66920546HCID 66920546, compoundYield 34.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 500 mg (1.14 mmol) of the compound of example 16, step 1, in THF (8 ml) was cooled to −78° C. with an acetone/dry ice bath. Within 10 min a solution of n-butyllithium (0.55 ml, 1.36 mmol, 2.5 M in hexane) was added followed by 0.36 ml (2.27 mmol) of 2-chloro-6-fluoro-benzyl bromide. The cooling bath was removed and the reaction mixture was allowed to warm up slowly to room temperature and stirred overnight. 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 216 mg of the title compound.

Workup

  1. customThe cooling bath was removed
  2. customThe mixture was quenched with water
  3. extractionextracted with EA
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified by preparative HPLC
  9. waitThe eluate was lyophilized overnight

Sources & evidence

ORD record
ord-4c6d6e091ed447a481f448852530ff3f
Source dataset
uspto-grants-2012_07
Patent number
US08211885B2

Reaction notes

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