Methanol → Methyl 4-fluoro-3-nitrobenzoate

HRID 1828183Notes

Reaction equation

HRID 1828183 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[C:14](Cl)(=O)C(Cl)=O.C(N(CC)CC)C.CO.C(=O)(O)[O-].[Na+]>ClCCl.CN(C)C=O>[CH3:14][O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([N+:11]([O-:13])=[O:12])[CH:4]=1

Participants

8

Reactant 5

HCID 887MethanolHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 679874-Fluoro-3-nitrobenzoic acidHCID 516892Sodium Bicarbonate

Product 1

HCID 5219721Methyl 4-fluoro-3-nitrobenzoateYield 98.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-fluoro-3-nitro-benzoic acid (25 g, 0.135 mol) in dichloromethane (250 ml) at 23° C. was added dimethylformamide (0.5 ml) followed by dropwise addition of oxalyl chloride (15 ml, 0.172 mol). After stirring for 2 hours an aliquot was removed and confirmed to be product by 1H NMR. The entire sample was then concentrated under reduced pressure, diluted with dichloromethane (250 ml) and cooled to 0° C. The sample was then treated with a solution of triethylamine (37 ml, 0.266 mol) and methyl alcohol (43 ml, 0.939 mol) in dichloromethane (50 ml) added dropwise over 30 minutes. The reaction was allowed to warm to 23° C. After 2 hours the reaction was poured onto aqueous sodium bicarbonate and extracted with dichloromethane. The organic layer was dried with sodium sulfate and concentrated in vacuo to give 26.5 g of 4-fluoro-3-nitro-benzoic acid methyl ester as a solid.

Workup

  1. customwas removed
  2. concentrationThe entire sample was then concentrated under reduced pressure
  3. additiondiluted with dichloromethane (250 ml)
  4. additionadded dropwise over 30 minutes
  5. temperatureto warm to 23° C
  6. extractionextracted with dichloromethane
  7. dry with materialThe organic layer was dried with sodium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-001cf9a8e5074dc49984b3dd277b4e9b
Source dataset
uspto-grants-2006_06
Patent number
US07056918B2

Reaction notes

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