Sodium Hydroxide → 7-Amino-3-methylphthalide

HRID 431299Notes

Reaction equation

HRID 431299 reaction equation
[CH3:1][CH:2]1[C:11]2[C:6](=[C:7]([N+:12]([O-])=O)[CH:8]=[CH:9][CH:10]=2)[C:4](=[O:5])[O:3]1.[OH-].[Na+].[N+](C1C=CC=C(C(O)C)C=1C(O)=O)([O-])=O.O.NN>C(O)=O.C(OCC)(=O)C.CCCCCC>[NH2:12][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[C:4](=[O:5])[O:3][CH:2]2[CH3:1]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 18763752HCID 18763752, compoundHCID 18763753HCID 18763753, compound

Product 1

HCID 4877817-Amino-3-methylphthalideYield 90.4%

Reagents, catalysts & solvents 2

HCID 284Formic AcidCatalystHCID 21226206Ethyl acetate hexaneSolvent

Procedure

2.37 g (12.2 mmol) of 3-methyl-7-nitro-3H-isobenzofuran-1-one (Example 4) are heated in 5 ml of 30% sodium hydroxide solution (49 mmol) for 1 hour at 90° C. until 2-nitro-6-(1-hydroxyethyl)-benzoic acid can be demonstrated almost quantitatively by TLC (mobile phase: ethyl acetate/hexane 3:1 plus 1 drop of formic acid). 1.2 ml (24.5 mmol) of hydrazine hydrate are then slowly added dropwise and the temperature is maintained for a further 4 hours. The cooled reaction mixture is then adjusted to a pH of 2 and is extracted with ethyl acetate. 1.8 g (90.4%) of crude 7-amino-3-methyl-3H-isobenzofuran-1-one are obtained; 1H-NMR (CDCl3): 7.37 ppm, t, 1H; 6.63 ppm, d, 1H; 6.61 ppm, d, 1H; 5.44 ppm, q, 1H; 5.22 ppm, b, 2H; 1.58 ppm, d, 3H.

Workup

  1. temperaturethe temperature is maintained for a further 4 hours
  2. customThe cooled reaction mixture
  3. extractionis extracted with ethyl acetate

Sources & evidence

ORD record
ord-3c66f5428d3f4012852fbce78c17a962
Source dataset
uspto-grants-2003_12
Patent number
US06657085B2

Reaction notes

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