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

HRID 2362970Notes

Reaction equation

HRID 2362970 reaction equation
[CH3:1][C:2]1([CH3:12])[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]([CH3:12])([CH3:1])[C:3]1=[O:11]

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 3131003,3-Dimethyl-1,3-dihydro-indol-2-one

Product 1

HCID 580466771-(3-Chloropropyl)-3,3-dimethylindolin-2-oneYield 87.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3,3-dimethylindolin-2-one (1.843 g, 11.43 mmol, 1 equiv) in N,N-dimethylformamide was cooled to 0° C. Sodium hydride (60% dispersion) (503 mg, 12.58 mmol, 1.1 equiv) was slowly added and the reaction was stirred as such until all bubbling had stopped. 1-bromo-3-chloropropane (3.37 ml, 34.3 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 light orange oil (2.38 g, 87%); 1H NMR (400 MHz, DMSO-d6): δ 1.26 (s, 6H); 1.98-2.14 (m, 2H); 3.65 (t, 2H, J=6 and 6.8 Hz); 3.77-3.81 (m, 2H); 7.02-7.07 (m, 2H); 7.24-7.28 (m, 1H); 7.33-7.35 (m, 1H); MS for C13H16ClNO m/z 237.99 (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-80d85fa3c8fe4ee6bf61a0fbc0eed294
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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