Triethylamine → (2,4-Bis-benzyloxy-5-isopropenyl-phenyl)-{4-[2-(2-methoxy-ethoxy)-ethoxy]-1,3-dihydro-isoindol-2-yl}-methanone

HRID 41433Notes

Reaction equation

HRID 41433 reaction equation
[CH2:1]([O:8][C:9]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:15]([C:26]([CH3:28])=[CH2:27])=[CH:14][C:10]=1[C:11]([OH:13])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:29](Cl)(=[O:33])[C:30](Cl)=[O:31].C([N:37]([CH2:40][CH3:41])[CH2:38][CH3:39])C>CN(C=O)C.C(Cl)Cl.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:15]([C:26]([CH3:28])=[CH2:27])=[CH:14][C:10]=1[C:11]([N:37]1[CH2:38][C:39]2[C:41](=[CH:3][CH:4]=[CH:5][C:6]=2[O:31][CH2:30][CH2:29][O:33][CH2:2][CH2:1][O:8][CH3:9])[CH2:40]1)=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 498640162,4-Bis(benzyloxy)-5-isopropenylbenzoic acid

Product 1

HCID 59263110(2,4-Bis-benzyloxy-5-isopropenyl-phenyl)-{4-[2-(2-methoxy-ethoxy)-ethoxy]-1,3-dihydro-isoindol-2-yl}-methanone

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2,4-bis-benzyloxy-5-isopropenyl-benzoic acid (96 mg, 0.26 mmol) and DMF (1 drop, cat.) in DCM (3 mL) was cooled in ice then treated with oxalyl chloride (112 μL, 1.28 mmol). After 2 hours the mixture was concentrated in vacuo then azeotroped with toluene. The resulting acid chloride was dissolved in DCM (4 mL) and added to a solution of 4-[2-(2-methoxy-ethoxy)-ethoxy]-2,3-dihydro-1H-isoindole (0.26 mmol, assuming a quantitative yield from the preceding step (debenzylation procedure C16)) and triethylamine (0.20 mL, 1.4 mmol) in DCM (1 mL). After 2 hours the mixture was diluted with ethyl acetate and washed with 1N hydrochloric acid, brine, sodium bicarbonate solution and brine. The organic phase was dried (MgSO4) and concentrated to give a black residue. This was partially purified by flash chromatography on silica (ethyl acetate/petrol gradient, 20-33%) to afford an impure sample of the intermediate (2,4-bis-benzyloxy-5-isopropenyl-phenyl)-{4-[2-(2-methoxy-ethoxy)-ethoxy]-1,3-dihydro-isoindol-2-yl}-methanone.

Workup

  1. concentrationAfter 2 hours the mixture was concentrated in vacuo
  2. customthen azeotroped with toluene
  3. dissolutionThe resulting acid chloride was dissolved in DCM (4 mL)
  4. additionadded to a solution of 4-[2-(2-methoxy-ethoxy)-ethoxy]-2,3-dihydro-1H-isoindole (0.26 mmol
  5. washwashed with 1N hydrochloric acid, brine, sodium bicarbonate solution and brine
  6. dry with materialThe organic phase was dried (MgSO4)
  7. concentrationconcentrated
  8. customto give a black residue
  9. customThis was partially purified by flash chromatography on silica (ethyl acetate/petrol gradient, 20-33%)

Sources & evidence

ORD record
ord-7f430b8ac74c49c29b3d0f15eb8dea6e
Source dataset
uspto-grants-2013_09
Patent number
US08530469B2

Reaction notes

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