Phosphorus oxychloride → HCID 12605980, compound

HRID 869457Notes

Reaction equation

HRID 869457 reaction equation
O[C:2]1[C:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:4]([CH3:7])[S:5][CH:6]=1.P(Cl)(Cl)([Cl:15])=O.C[C:19]([O-:21])=O.[Na+]>CN(C=O)C>[Cl:15][C:2]1[C:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:4]([CH3:7])[S:5][C:6]=1[CH:19]=[O:21]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 298463ethyl 4-hydroxy-2-methylthiophene-3-carboxylateHCID 517045Sodium Acetate

Product 1

HCID 12605980HCID 12605980, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of ethyl 4-hydroxy-2-methylthiophene-3-carboxylate (F-3) (20.0 g, 0.11 mol, 1.0 eq) in DMF (150 mL) at −20° C. under argon, phosphoryl chloride (49.4 g, 0.32 mol, 3.0 eq) is added dropwise while keeping the reaction temperature below 10° C. The resulting mixture is stirred at RT for 30 min and then at 80° C. for 1 h. The reaction mixture is cooled to RT and poured into ice-water (800 mL). The resulting mixture is neutralized with NaOAc to adjust the pH to 7-8. The precipitate is collected by filtration, rinsed with H2O (150 mL), and dried in vacuo. The product is purified by flash column chromatography on silica gel (5% ethyl acetate-petroether) to afford the product, ethyl 4-chloro-5-formyl-2-methylthiophene-3-carboxylate (F-4).

Workup

  1. customthe reaction temperature below 10° C
  2. waitat 80° C. for 1 h
  3. temperatureThe reaction mixture is cooled to RT
  4. filtrationThe precipitate is collected by filtration
  5. washrinsed with H2O (150 mL)
  6. customdried in vacuo
  7. customThe product is purified by flash column chromatography on silica gel (5% ethyl acetate-petroether)

Sources & evidence

ORD record
ord-bdb671e05a304e0da9c540f9dbebeaf7
Source dataset
uspto-grants-2015_03
Patent number
US08969363B2

Reaction notes

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