p-Toluenesulfonic acid → 2-[(3aS,4R,7aR)-2,2-dimethylhexahydro-1,3-benzodioxol-4-yl]-1H-isoindole-1,3(2H)-dione

HRID 1951568Notes

Reaction equation

HRID 1951568 reaction equation
[OH:1][C@@H:2]1[C@H:7]([OH:8])[CH2:6][CH2:5][CH2:4][C@H:3]1[N:9]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]1=[O:19].[C:20]1(C)[CH:25]=CC(S(O)(=O)=O)=C[CH:21]=1>CC(C)=O>[CH3:21][C:20]1([CH3:25])[O:8][C@@H:7]2[CH2:6][CH2:5][CH2:4][C@@H:3]([N:9]3[C:10](=[O:19])[C:11]4[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=4)[C:17]3=[O:18])[C@@H:2]2[O:1]1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 583696512-[(1R,2S,3R)-2,3-dihydroxycyclohexyl]-1H-isoindole-1,3(2H)-dione

Product 1

HCID 583696542-[(3aS,4R,7aR)-2,2-dimethylhexahydro-1,3-benzodioxol-4-yl]-1H-isoindole-1,3(2H)-dioneYield 96.8%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 2-[(1R,2S,3R)-2,3-dihydroxycyclohexyl]-1H-isoindole-1,3(2H)-dione (19) (50.0 g, 191.4 mmol) and 2,2-methoxypropane (500 mL, 4.07 mol) in acetone (500 mL), a catalytic amount of p-toluenesulfonic acid was added and the resulting reaction mixture was stirred at room temperature for 3 h. The reaction was quenched with saturated Na2CO3 solution to adjust the pH to 10 and the solvent was removed. Water (750 mL) was added to the residue and extracted with ethyl acetate (2×750, 500 mL). The organics were combined, dried over Na2SO4 and concentrated to give the desired product as a white solid (55.8 g, 96.8% yield). LC/MS [Method B: rt: 6.16 min; m/z: 302 (M+1)].

Workup

  1. customthe resulting reaction mixture
  2. customThe reaction was quenched with saturated Na2CO3 solution
  3. customthe solvent was removed
  4. additionWater (750 mL) was added to the residue
  5. extractionextracted with ethyl acetate (2×750, 500 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f034e554b961496ab20c397749b823c0
Source dataset
uspto-grants-2013_03
Patent number
US08404725B2

Reaction notes

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