Methanesulfonic Acid → 6-Fluoro-1-benzopyran-2-carboxylic acid methyl ester

HRID 875253Notes

Reaction equation

HRID 875253 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][C:9]([C:11]([OH:13])=[O:12])=[CH:8][C:7](=O)[C:6]=2[CH:15]=1.[H][H].[CH3:18]S(O)(=O)=O>C1COCC1.[Pd]>[CH3:18][O:13][C:11]([CH:9]1[CH:8]=[CH:7][C:6]2[CH:15]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:10]1)=[O:12]

Participants

6

Reactant 3

HCID 6395Methanesulfonic AcidHCID 40960466-fluoro-4-oxo-4H-chromene-2-carboxylic acidHCID 178418361HCID 178418361, compound2×

Product 1

HCID 673938016-Fluoro-1-benzopyran-2-carboxylic acid methyl esterYield 480.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22.5 °C

Procedure

20 g of 6-fluoro-4-oxo-4H-1-benzopyran-2-carboxylic acid (96 mmol) were hydrogenated under 4 bars of hydrogen in 200 ml THF with 2 g of methanesulfonic acid (20 mmol) and 2 g of 5% Pd on charcoal (Type Escat 112, Engelhard) at 45-55° C. until consumption of hydrogen was no longer observed. The reaction progress was monitored by TLC. The catalyst was then removed by filtration and the reaction mixture concentrated to 40 ml under reduced pressure. 100 ml of methanol were then added and the mixture (solution) was stirred at 20-25° C. until less than 1% of 6-fluoro-3,4-dihydro-2H-chromen-2-carboxylic acid was detected (TLC). The solution was then concentrated under reduced pressure and the residue was dissolved in 60 ml of THF then concentrated under reduced pressure to remove water by azeotropic distillation to give 20 g of the title compound (yield: 100%).

Workup

  1. customThe catalyst was then removed by filtration
  2. concentrationthe reaction mixture concentrated to 40 ml under reduced pressure
  3. addition100 ml of methanol were then added
  4. concentrationThe solution was then concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in 60 ml of THF
  6. concentrationthen concentrated under reduced pressure
  7. customto remove water
  8. distillationby azeotropic distillation

Sources & evidence

ORD record
ord-eca4c2cc50104622bfed2f5d2d9e7a83
Source dataset
uspto-grants-2015_03
Patent number
US08981127B2

Reaction notes

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