Water → 5-Methoxy-3,3-dimethylisoindolin-1-one

HRID 1737308Notes

Reaction equation

HRID 1737308 reaction equation
[N:1]([C:4]([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH3:14])[CH:8]=1)([CH3:6])[CH3:5])=[C:2]=[O:3].O>ClCCCl>[CH3:14][O:13][C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][CH:10]=1)[C:2](=[O:3])[NH:1][C:4]2([CH3:6])[CH3:5]

Participants

4

Reactant 2

HCID 962WaterHCID 10559617Benzene, 1-(1-isocyanato-1-methylethyl)-3-methoxy-

Product 1

HCID 105838765-Methoxy-3,3-dimethylisoindolin-1-one

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To an ice-cold slurry of FeCl3 (35.69 g, 220 mmol) in dry DCE (800 mL) is added a solution of isocyanate 56 (19.12 g, 100.0 mmol) in the same solvent (100 mL) over 45 min. After completion of the addition, GC analysis of an aliquot indicates complete reaction. Water (600 mL) is added and the resulting mixture is stirred vigorously. The layers are separated, and the organic phase is washed 2×1 L with 1 M tartaric acid solution and once with brine. The solution is dried (MgSO4), filtered and evaporated to a dark liquid. This is purified by FC (1:4 hexane/EtOAc, then EtOAc) to provide the 5-methoxy isoindolone 57 as a pale yellow solid, mp 146-147° C., 7.38 g (39%), and the regioisomeric 7-methoxy isoindolone 61 as a yellow solid, mp 155-158° C., 2.85 g (15%). For 57: 1H NMR (CDCl3) 7.74 (d, 1, J=8.5), 7.00-6.95 (m, 1), 6.85 (d, 1, J=2.2), 3.89 (s, 3), 1.54 (s, 6); 13C NMR (CDCl3) 169.57, 163.19, 155.44, 125.31, 123.14, 114.18, 105.92, 58.64, 55.61, 27.81; MS (MW=191.2, EI, eE=70 eV) m/z 191 (M+), 176 (base peak), 161, 133, 118, 88, 77, 63, 42.

Workup

  1. additionAfter completion of the addition, GC analysis of an aliquot
  2. customreaction
  3. customThe layers are separated
  4. washthe organic phase is washed 2×1 L with 1 M tartaric acid solution
  5. dry with materialThe solution is dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated to a dark liquid
  8. customThis is purified by FC (1:4 hexane/EtOAc

Sources & evidence

ORD record
ord-48d9ffe637354a6da76ce2f3380506fb
Source dataset
uspto-grants-1999_10
Patent number
US05962469

Reaction notes

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