p-Toluenesulfonic acid → Isocoumarin

HRID 233624Notes

Reaction equation

HRID 233624 reaction equation
CC(C[AlH]CC(C)C)C.[O-]S([O-])(=O)=O.[Na+].[Na+].[CH:17](OC)([O:20][CH3:21])[O:18]C.[CH3:24][C:25]1[CH:26]=[CH:27][C:28](S(O)(=O)=O)=[CH:29][CH:30]=1>C1(C)C=CC=CC=1.CO>[C:17]1([C:26]2[C:25](=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:24]=[CH:21][O:20]1)=[O:18]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 14487Diisobutylaluminum hydrideHCID 24436Sodium Sulfate

Product 1

HCID 68108Isocoumarin

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

To a stirred solution of the isocaumarin from step 3 above (9.4 mg, 0.4 mmol) in 8 ml of toluene was added dropwise a solution of DIBAL-H (1M, 0.50 ml, 0.50 mmol) at -78° C. under argon. The resulting mixture was stirred at -78° C. for 1.5 hour before Na2SO4 10 H2O (100 mg, 0.31 mmol). After the reaction was warmed to room temperature, it was filtered to remove the solids, and washed with acetone. The filtrate was evaporated to give an oily residue which contained the corresponding lactol. Without further purification, the residue was treated with 5 ml of CH3OH, 1 ml of CH(OMe)3, and PTSA (30 mg, 0.16 mmol) at room temperature for 10 minutes. The solvents were removed by rotavapor and the residue was purified by flash chromatography with hexane and ethyl acetate (7:3) to give pure title isocoumarin (65 mg, 0.26 mmol) in 65% overall yield. 1H NMR (CDCl3) δ:2.47 (1H, dd, J=17.2, 12.0 Hz), 2.85 (1H, dd, J=17.2, 3.6 Hz), 3.56 (3H, s), 3.78 (3H, s), 3.82 (3H, s), 4.63 (1H, m), 5.24 (1H, dt, J=10.6, 1.4 Hz), 5.43 (1H, dt, J=17.3, 1.4 Hz), 5.63 (1H, s), 6.05 (1H, m), 6.70 (1H, d, J=8.9 Hz), 6.76 (1H, d, J=8.9 Hz).

Workup

  1. filtrationit was filtered
  2. customto remove the solids
  3. washwashed with acetone
  4. customThe filtrate was evaporated
  5. customto give an oily residue which
  6. customWithout further purification
  7. customThe solvents were removed by rotavapor
  8. customthe residue was purified by flash chromatography with hexane and ethyl acetate (7:3)

Sources & evidence

ORD record
ord-31eea2d6830841438339abc558197433
Source dataset
uspto-grants-1997_01
Patent number
US05593970

Reaction notes

Loading…