Carbon Dioxide → 2-Phenylamino-4-fluoromethyl-6-cyclopropylpyrimidine

HRID 465359Notes

Reaction equation

HRID 465359 reaction equation
C(N(S(F)(F)[F:7])CC)C.[C:10]1([NH:16][C:17]2[N:22]=[C:21]([CH2:23]O)[CH:20]=[C:19]([CH:25]3[CH2:27][CH2:26]3)[N:18]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)([O-])O.[Na+].C(=O)=O>ClCCl>[C:10]1([NH:16][C:17]2[N:22]=[C:21]([CH2:23][F:7])[CH:20]=[C:19]([CH:25]3[CH2:27][CH2:26]3)[N:18]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 198740942-Anilino-4-hydroxymethyl-6-cyclopropylpyrimidine

Product 1

HCID 198740872-Phenylamino-4-fluoromethyl-6-cyclopropylpyrimidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

6.1 g (37.8 mmol) of diethylaminosulfur trifluoride in 15 ml of dichloromethane are slowly added dropwise within a period of one hour, with stirring, to a suspension of 9.1 g (37.8 mmol) of 2-phenylamino-4-hydroxymethyl-6-cyclopropylpyrimidine in 80 ml of dichloromethane. After the addition of 50 ml of ice-water, 50 ml of 10% aqueous sodium hydrogen carbonate solution are added dropwise. When the evolution of carbon dioxide has ceased, the organic phase is separated off and the aqueous phase is extracted twice with 20 ml of dichloromethane each time. The combined dichloromethane solutions are washed with 15 ml of water, dried over sodium sulfate and filtered, and the solvent is evaporated. The black oil which remains is purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether (b.p. 50°-70° ); 5/3/1/1). After the eluant mixture has been evaporated off, the yellow oil is diluted with 20 ml of petroleum ether (b.p. 50°-70° C.) and crystallised at reduced temperature. The yellowish crystals melt at 50°-52° C. Yield: 4.9 g (20.1 mmol; 53% of the theoretical yield).

Workup

  1. additionare added dropwise
  2. customthe organic phase is separated off
  3. extractionthe aqueous phase is extracted twice with 20 ml of dichloromethane each time
  4. washThe combined dichloromethane solutions are washed with 15 ml of water
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent is evaporated
  8. customThe black oil which remains is purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether (b.p. 50°-70° ); 5/3/1/1)
  9. customAfter the eluant mixture has been evaporated off
  10. additionthe yellow oil is diluted with 20 ml of petroleum ether (b.p. 50°-70° C.)
  11. customcrystallised at reduced temperature
  12. custommelt at 50°-52° C
  13. custom53% of the theoretical yield)

Sources & evidence

ORD record
ord-aeb6e0920a8f47739ccc60f8c17cb307
Source dataset
uspto-grants-1992_10
Patent number
US05153200

Reaction notes

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