Dimethyl Sulfate → Methyl 2-hydroxy-3-nitrobenzoate

HRID 1671012Notes

Reaction equation

HRID 1671012 reaction equation
[OH:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:14]([O-])([O-])=O.[K+].[K+].S(OC)(OC)(=O)=O>CN(C=O)C>[OH:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([O:6][CH3:14])=[O:5]

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 68073-Nitrosalicylic acidHCID 11430Potassium Carbonate

Product 1

HCID 596904Methyl 2-hydroxy-3-nitrobenzoateYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-hydroxy-3-nitrobenzoic acid (25 g, 136 mmol) in DMF (125 mL) was added K2CO3 (37.8 g, 273 mmol). Then dimethyl sulfate (48.2 g, 382 mmol) was added dropwise to the mixture at rt. The mixture was stirred at rt overnight. Then the reaction was quenched by the addition of the saturated aqueous NH4Cl (800 mL) at 0° C. The reaction mixture was extracted with EtOAc (500 mL×2). The combined organic layers were washed with water successively, dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound of Step A (26.8 g, 99.6% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.10-8.18 (m, 2H), 7.97-8.03 (br, 1H), 6.95-7.03 (m, 1H), 4.00 (s, 3H).

Workup

  1. customThen the reaction was quenched by the addition of the saturated aqueous NH4Cl (800 mL) at 0° C
  2. extractionThe reaction mixture was extracted with EtOAc (500 mL×2)
  3. washThe combined organic layers were washed with water successively
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-151ee7a2b53d4a72817b275e49df6eb4
Source dataset
uspto-grants-2011_08
Patent number
US07994185B2

Reaction notes

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