Phosphorus oxychloride → HCID 18536895, compound

HRID 2298606Notes

Reaction equation

HRID 2298606 reaction equation
[CH3:1][S:2][C:3]1[S:7][C:6]([C:8]([O:10][CH3:11])=[O:9])=[CH:5][C:4]=1[C:12](=[O:23])[NH:13][CH:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:15]=O.P(Cl)(Cl)(Cl)=O.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:1][S:2][C:3]1[S:7][C:6]([C:8]([O:10][CH3:11])=[O:9])=[CH:5][C:4]=1[C:12]1[O:23][CH:15]=[C:14]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:13]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 18537424HCID 18537424, compound

Product 1

HCID 18536895HCID 18536895, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled (0° C.) solution of 465 mg (1.33 mmol) methyl 5-methylthio-4-[N-(2-oxo-1-phenylethyl)carbamoyl]thiophene-2-carboxylate (as prepared in the previous step) in 6 mL of anhyd DMF was added 186 μL (2.00 mmol) of phosphorus oxychloride. After stirring for 14 h at room temperature, the mixture was treated with 10 mL of saturated NaHCO3 and concentrated to dryness under high vacuum. The resulting residue was partitioned between 80 mL of EtOAc and 60 mL of water. The aqueous layer was extracted with EtOAc (2×10 mL) and the combined organic phases washed with brine (60 mL), and dried over Na2SO4. The resulting 406 mg of amber-colored solid was recrystallized from CH2Cl2—Et2O to remove the majority of a polar impurity as a cream-colored solid. The remaining mother liquors were chromatographed on a 10 g silica SPE column (Waters Sep-Pak) with a gradient of 40-100% CH2Cl2-hexane and the resulting residue triturated with Et2O-hexane (2:1)) to afford the title compound as a light beige solid (114 mg, 26%). 1H-NMR (300 MHz, CDCl3) δ8.24 (s, 1H), 7.93 (s, 1H), 7.83 (m, 2H), 7.43 (m, 2H), 7.33 (m, 1H), 3.91 (s, 3H), and 2.72 (s, 3H). Mass spectrum (ESI) calcd. for C16H13NO3S2: 332.0 (M+H). Found: 332.2.

Workup

  1. concentrationconcentrated to dryness under high vacuum
  2. customThe resulting residue was partitioned between 80 mL of EtOAc and 60 mL of water
  3. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  4. washthe combined organic phases washed with brine (60 mL)
  5. dry with materialdried over Na2SO4
  6. customThe resulting 406 mg of amber-colored solid was recrystallized from CH2Cl2—Et2O
  7. customto remove the majority of a polar impurity as a cream-colored solid
  8. customThe remaining mother liquors were chromatographed on a 10 g silica SPE column (Waters Sep-Pak) with a gradient of 40-100% CH2Cl2-hexane
  9. customthe resulting residue triturated with Et2O-hexane (2:1))

Sources & evidence

ORD record
ord-bcbc7bcbdfc54fd895927de9e19f4ac6
Source dataset
uspto-grants-2002_12
Patent number
US06492403B1

Reaction notes

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