Diethyl Ether → 2-(3-(3-(Benzyloxy)phenyl)propyl)isoindoline-1,3-dione

HRID 1523147Notes

Reaction equation

HRID 1523147 reaction equation
CCOCC.[OH:6][C:7]1[CH:8]=[C:9]([CH2:13][CH2:14][CH2:15][N:16]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]2=[O:26])[CH:10]=[CH:11][CH:12]=1.[CH2:27](Br)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1>[CH2:27]([O:6][C:7]1[CH:8]=[C:9]([CH2:13][CH2:14][CH2:15][N:16]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]2=[O:26])[CH:10]=[CH:11][CH:12]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 580275422-[3-(3-Hydroxyphenyl)propyl]isoindole-1,3-dione

Product 1

HCID 673166422-(3-(3-(Benzyloxy)phenyl)propyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

Instead of a Mitsunobu reaction, the ether was formed by alkylation as described. A suspension of phenol 58 (1 g, 3.5 mmol), benzyl bromide (0.3 mL, 3.5 mmol), cesium carbonate (1.158 g, 3.5 mmol) in NMP (3.5 mL) was heated at 70° C. for 24 h. The reaction mixture was quenched by the addition of water, extracted with DCM, washed with water, and dried over anhy. Na2SO4. Filtration and concentration under reduced pressure gave the crude product, which was purified by flash chromatography (hexane-ethyl acetate (0-30%) gradients) to give 2-(3-(3-(benzyloxy)phenyl)propyl) isoindoline-1,3-dione as a white solid. Yield (0.708 g, 55%): 1H NMR (400 MHz, DMSO-d6) δ 7.81-7.84 (m, 2H), 7.69-7.72 (m, 2H), 7.30-7.44 (m, 5H), 7.13-7.18 (m, 1H), 6.83-6.85 (m, 1H), 6.80 (d, J=7.6 Hz, 1H), 6.74 (dd, J=7.8, 2.0, 1H), 5.03 (s, 2H), 3.74 (t, J=7.2 Hz, 2H), 2.67 (t, J=7.6 Hz, 2H), 2.0-2.08 (m, 2H).

Workup

  1. customInstead of a Mitsunobu reaction
  2. customThe reaction mixture was quenched by the addition of water
  3. extractionextracted with DCM
  4. washwashed with water
  5. customdried over anhy
  6. filtrationFiltration and concentration under reduced pressure
  7. customgave the crude product, which
  8. customwas purified by flash chromatography (hexane-ethyl acetate (0-30%) gradients)

Sources & evidence

ORD record
ord-82dca1858bc049838bbec7ee395562ec
Source dataset
uspto-grants-2015_07
Patent number
US09079825B2

Reaction notes

Loading…