Benzylamine → Methyl 2-benzylisoindoline-5-carboxylate

HRID 1808326Notes

Reaction equation

HRID 1808326 reaction equation
Br[CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH2:13]Br)[C:6]([O:8][CH3:9])=[O:7].[CH2:15]([NH2:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1C=CC=CC=1>[CH2:15]([N:22]1[CH2:2][C:3]2[C:12](=[CH:11][CH:10]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH:4]=2)[CH2:13]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

4

Reactant 2

HCID 7504BenzylamineHCID 2736819Methyl 3,4-bis(bromomethyl)benzoate

Product 1

HCID 23301778Methyl 2-benzylisoindoline-5-carboxylateYield 28.5%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

TEA was added at room temperature, in the course of 15 minutes, to a solution of methyl 3,4-bis(bromomethyl)benzoate (9.3 g; 1 equiv.) and benzylamine (4.3 g; 1.4 equiv.) in 83.7 ml of benzene. The resulting reaction mixture was first stirred for 30 minutes at room temperature and then heated for 20 hours at reflux (110-120° C.). When the conversion was complete, the reaction mixture was cooled to room temperature and filtered. The filtrate was taken up in 100 ml of dichloromethane and washed 2× with 5% sodium carbonate solution. The combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure. Purification by column chromatography (silica gel, 5% ethyl acetate/hexane) yielded methyl 2-benzylisoindoline-5-carboxylate (2.2 g; 28.3%) in the form of a solid.

Workup

  1. customThe resulting reaction mixture
  2. temperatureheated for 20 hours
  3. temperatureat reflux (110-120° C.)
  4. temperaturethe reaction mixture was cooled to room temperature
  5. filtrationfiltered
  6. washwashed 2× with 5% sodium carbonate solution
  7. dry with materialThe combined organic phases were dried over sodium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customPurification by column chromatography (silica gel, 5% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-0a4cb9e67b4a4a898ed770844f199962
Source dataset
uspto-grants-2013_01
Patent number
US08357717B2

Reaction notes

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