Hydrogen Bromide → 4,7-Difluoro-2,3-dihydro-1h-isoindole

HRID 41394Notes

Reaction equation

HRID 41394 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][N:5](S(C1C=CC(C)=CC=1)(=O)=O)[CH2:6]2.C1(O)C=CC=CC=1.Br>O.C(O)(=O)CC>[F:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][NH:5][CH2:6]2

Participants

6

Reactant 3

HCID 260Hydrogen BromideHCID 996PhenolHCID 593822484,7-Difluoro-2-(toluene-4-sulfonyl)isoindoline

Product 1

HCID 576016864,7-Difluoro-2,3-dihydro-1h-isoindoleYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1032Propionic AcidSolvent

Procedure

A mixture of 4,7-difluoro-2-(toluene-4-sulfonyl)isoindoline (2.36 g, 7.64 mmol), phenol (2.36 g, 25.11 mmol), 48% hydrogen bromide in water (20 ml) and propionic acid (4 ml) was stirred and held at reflux for 6 hours. Upon cooling to room temperature water (50 ml) was added and the mixture extracted with diethyl ether (2×100 ml). The aqueous layer was basified by the addition of 2M sodium hydroxide and was extracted with diethyl ether (3×100 ml). The combined extracts were evaporated to dryness in vacuo to afford 4,7-difluoroisoindoline (586 mg, 50%) as a brown oil that solidified upon standing. 1H NMR (DMSO-d6) 7.06 (2H, dd), 4.12 (4H, s). MS: [M+H]+ 156.

Workup

  1. temperatureat reflux for 6 hours
  2. additionwas added
  3. extractionthe mixture extracted with diethyl ether (2×100 ml)
  4. additionThe aqueous layer was basified by the addition of 2M sodium hydroxide
  5. extractionwas extracted with diethyl ether (3×100 ml)
  6. customThe combined extracts were evaporated to dryness in vacuo

Sources & evidence

ORD record
ord-dffd432e917040c99fd4e41c096a9a7b
Source dataset
uspto-grants-2013_09
Patent number
US08530469B2

Reaction notes

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