Carbon Dioxide → 5-Fluoro-4-thiouracil

HRID 1405984Notes

Reaction equation

HRID 1405984 reaction equation
P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:2].[F:15][C:16]1[C:17](=O)[NH:18][C:19](=[O:22])[NH:20][CH:21]=1.C(=O)([O-])O.[Na+].C(=O)=O>COCCOCCOC.O>[F:15][C:16]1[C:17](=[S:2])[NH:18][C:19](=[O:22])[NH:20][CH:21]=1

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 33855-FluorouracilHCID 14817Phosphorus sulfide (P2S5)HCID 516892Sodium Bicarbonate

Product 1

HCID 27812135-Fluoro-4-thiouracilYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8150DiglymeSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of phosphorus pentasulfide (102.6 g, 0.46 mol) in diglyme (1 L) was added 5-fluoropyrimidine-2,4(1H,3H)-dione (30 g, 0.23 mol). Solid sodium hydrogen carbonate (NaHCO3; 77.3 g, 1.04 mol) was added at a rate determined by the evolution of carbon dioxide. The reaction mixture was stirred overnight at 110° C. The yellow mixture was cooled and poured into 1 L of cold water. The precipitated solid product was isolated by filtration and purified by normal phase chromatography (gradient, 10 to 50% EtOAc/Petroleum ether) to give 5-fluoro-4-thioxo-3,4-dihydropyrimidin-2(1H)-one (13.4 g, 40%) as a yellow solid: mp 254-255° C.; 1H NMR (301 MHz, DMSO-d6) δ 7.81 (d, J=4.0 Hz, 1H); ESIMS m/z 145 ([M−H]−).

Workup

  1. temperatureThe yellow mixture was cooled
  2. customThe precipitated solid product was isolated by filtration
  3. custompurified by normal phase chromatography (gradient, 10 to 50% EtOAc/Petroleum ether)

Sources & evidence

ORD record
ord-6e0567f0cc224db58437a4862a279ac0
Source dataset
uspto-grants-2014_12
Patent number
US08916579B2

Reaction notes

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