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

HRID 1924370Notes

Reaction equation

HRID 1924370 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 DCE (150 mL) was placed in a 1 L round bottom flask under nitrogen. To this was attached an addition funnel containing a solution of 1-chloroethyl chloroformate (7.51 mL, 69.6 mmol) in DCE. 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 removed by evaporation. Methanol (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 sodium hydroxide then extracted with DCM (4×250 mL). The combined organic extracts were dried with anhydrous sodium sulfate, filtered and the filtrate evaporated. The remaining residue was subjected to flash column chromatography eluting with DCM/MeOH/ammonium hydroxide 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. temperaturethen heated
  6. temperatureto reflux for 45 min
  7. temperatureThe contents of the reaction flask were cooled to RT
  8. customthe solvent removed by evaporation
  9. additionMethanol (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 DCM (4×250 mL)
  17. dry with materialThe combined organic extracts were dried with anhydrous sodium sulfate
  18. filtrationfiltered
  19. customthe filtrate evaporated
  20. washeluting with DCM/MeOH/ammonium hydroxide 97/3/0.3 to 95/5/0.5
  21. customEvaporation of fractions

Sources & evidence

ORD record
ord-437f7a3d3fad4048a981395c89630420
Source dataset
uspto-grants-2012_05
Patent number
US08178520B2

Reaction notes

Loading…