1-Bromo-3-chloropropane → 1-(3-Chloropropyl)-3,3-difluoroindolin-2-one

HRID 2362968Notes

Reaction equation

HRID 2362968 reaction equation
[F:1][C:2]1([F:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][C:3]1=[O:11].[H-].[Na+].Br[CH2:16][CH2:17][CH2:18][Cl:19]>CN(C)C=O>[Cl:19][CH2:18][CH2:17][CH2:16][N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2]([F:1])([F:12])[C:3]1=[O:11]

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 53238213,3-Difluoroindolin-2-one

Product 1

HCID 580466161-(3-Chloropropyl)-3,3-difluoroindolin-2-oneYield 100.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3,3-difluoroindolin-2-one (836.6 mg, 4.95 mmol, 1 equiv) in N,N-dimethylformamide was cooled to 0° C. Sodium hydride (60% dispersion) (217.6 mg, 5.44 mmol, 1.1 equiv) was slowly added and the reaction was stirred as such until all bubbling had stopped. 1-bromo-3-chloropropane (1.46 ml, 14.85 mmol, 3 equiv) was added to the reaction mixture in one portion. The reaction was allowed to warm to ambient temperature and stirred as such for 16 h. The crude mixture was partitioned between ethyl acetate and water. The organic layer was dried over MgSO4, filtered, concentrated, and the residue was purified using the Biotage flash chromatography system (SNAP 50 g cartridge, Rf=0.5, gradient—5%-30% ethyl acetate in hexanes) to afford the title compound as a yellow oil (1.22 g, quant); MS for C11H10ClF2NO m/z 247.01 (M+H)+.

Workup

  1. stirringstirred as such for 16 h
  2. customThe crude mixture was partitioned between ethyl acetate and water
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified

Sources & evidence

ORD record
ord-44a874f02d6444d5a552590e7801e90b
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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