Sodium borohydride → 7-methoxy-3H-isobenzofuran-1-one

HRID 505253Notes

Reaction equation

HRID 505253 reaction equation
[BH4-].[Na+].C(N(CC)[C:6](=[O:17])[C:7]1[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[CH:9][C:8]=1[CH:15]=[O:16])C>CO>[CH3:14][O:13][C:12]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:7]=1[C:6](=[O:17])[O:16][CH2:15]2

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 12460617N,N-Diethyl-2-formyl-6-methoxybenzamide

Product 1

HCID 109865837-methoxy-3H-isobenzofuran-1-oneYield 98%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Solid sodium borohydride (14.02 g, 370.5 mmol, 1.75 equiv) was added in portions to a solution of N,N-diethyl-2-formyl-6-methoxy-benzamide (49.81 g, 211.7 mmol) in methanol (800 ml) at 0° C. After complete addition, stirring was continued at room temperature for 30 minutes, until TLC analysis indicated complete consumption of starting material. The reaction mixture was cooled to 0° C., and 6N aqueous HCl (134 ml) was carefully added. The solution was heated to 90° C. for 90 minutes. After cooling, volatiles were removed in vacuo. The residue was taken up in water (500 ml) and extracted four times with EtOAc (1.6 liter in total). The combined organic layers were washed with brine (2×100 ml), dried over Na2SO4, filtered and concentrated in vacuo to afford the title compound (33.92 g, 98%) in adequate purity for direct use in the next transformation. 1H NMR (400 MHz, CDCl3): δ=7.60 (t, J=8.4 Hz, 1H), 7.00 (d, J=7.6 Hz, 1H), 6.91 (d, J=8.3 Hz, 1H), 5.22 (s, 2H), 3.98 (s, 3H). MS (ES+): 165 (M+H)+.

Workup

  1. additionAfter complete addition
  2. customconsumption of starting material
  3. addition6N aqueous HCl (134 ml) was carefully added
  4. temperatureThe solution was heated to 90° C. for 90 minutes
  5. temperatureAfter cooling
  6. customvolatiles were removed in vacuo
  7. extractionextracted four times with EtOAc (1.6 liter in total)
  8. washThe combined organic layers were washed with brine (2×100 ml)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-72c13594d681448b8837afb42031dc51
Source dataset
uspto-grants-2010_08
Patent number
US07781438B2

Reaction notes

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