1-Chloroethyl chloroformate → 4-Ethenyl-2,3-dihydro-1H-isoindole

HRID 2045700Notes

Reaction equation

HRID 2045700 reaction equation
C([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[CH:17]=[CH2:18])[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>ClCCCl>[CH:17]([C:14]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:15]=1[CH2:16][NH:8][CH2:9]2)=[CH2:18]

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 574311892-Benzyl-4-vinylisoindoline

Product 1

HCID 534871884-Ethenyl-2,3-dihydro-1H-isoindoleYield 71%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

A solution of 2-benzyl-4-vinylisoindoline (58 mmol) in 1,2-dichloroethane (150 mL) was placed in a 1 L round-bottom flask under nitrogen. An addition funnel containing a solution of 1-chloroethyl chloroformate (7.51 mL, 69.6 mmol) in 1,2-dichloroethane was attached to the reaction flask. The reaction flask was cooled in an ice bath, and the contents of the addition funnel were added dropwise over 20 min, keeping the internal reaction temperature <5° C. After the addition was complete, the reaction flask was allowed to warm to RT, then heated to reflux for 45 min. The contents of the reaction flask were cooled to RT, then the solvent was removed by evaporation. MeOH (200 mL) was added, and the contents of the reaction flask were heated to reflux for 30 min. The reaction flask was cooled, and the solvent removed by evaporation. Water (200 mL) was added, and the resulting mixture washed with EtOAc (2×250 mL). The aqueous layer was made basic with 2N NaOH then extracted with methylene chloride (4×250 mL). The combined organic extracts were dried with anhydrous Na2SO4, filtered and the filtrate evaporated. The remaining residue was subjected to flash column chromatography eluting with methylene chloride/MeOH/NH4OH 97/3/0.3 to 95/5/0.5. Evaporation of fractions gave the title compound as a brown oil, 6.00 g (41.4 mmol, 71% yield for two steps). LRMS (ESI) m/z 146 [(M+H)+; calcd for C10H12N: 146].

Workup

  1. temperatureThe reaction flask was cooled in an ice bath
  2. additionthe contents of the addition funnel were added dropwise over 20 min
  3. customthe internal reaction temperature <5° C
  4. additionAfter the addition
  5. temperatureheated
  6. temperatureto reflux for 45 min
  7. temperatureThe contents of the reaction flask were cooled to RT
  8. customthe solvent was removed by evaporation
  9. additionMeOH (200 mL) was added
  10. temperaturethe contents of the reaction flask were heated
  11. temperatureto reflux for 30 min
  12. temperatureThe reaction flask was cooled
  13. customthe solvent removed by evaporation
  14. additionWater (200 mL) was added
  15. washthe resulting mixture washed with EtOAc (2×250 mL)
  16. extractionthen extracted with methylene chloride (4×250 mL)
  17. dry with materialThe combined organic extracts were dried with anhydrous Na2SO4
  18. filtrationfiltered
  19. customthe filtrate evaporated
  20. washeluting with methylene chloride/MeOH/NH4OH 97/3/0.3 to 95/5/0.5
  21. customEvaporation of fractions

Sources & evidence

ORD record
ord-a3e18ae1494f41dabe12915a8894be21
Source dataset
uspto-grants-2013_11
Patent number
US08591878B2

Reaction notes

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