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

HRID 74354

Reaction equation

HRID 74354 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-5b72be5d12984ac3b3ad52285c35b1d9
Source dataset
uspto-grants-2014_09
Patent number
US08829244B2

Linked notes

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