Phosphoric Acid → 2-(Trifluoromethyl)pyrimidin-5-yl trifluoromethanesulfonate

HRID 643489Notes

Reaction equation

HRID 643489 reaction equation
S([O:8][S:9]([C:12]([F:15])([F:14])[F:13])(=[O:11])=[O:10])(C(F)(F)F)(=O)=O.[F:16][C:17]([F:26])([F:25])[C:18]1[N:23]=[CH:22][C:21](O)=[CH:20][N:19]=1.CCN(C(C)C)C(C)C.P(=O)(O)(O)O>C(Cl)Cl.O>[F:15][C:12]([F:13])([F:14])[S:9]([O:8][C:21]1[CH:20]=[N:19][C:18]([C:17]([F:26])([F:25])[F:16])=[N:23][CH:22]=1)(=[O:10])=[O:11]

Participants

7

Reactant 4

HCID 1004Phosphoric AcidHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 135906802-(Trifluoromethyl)pyrimidin-5-ol

Product 1

HCID 866151602-(Trifluoromethyl)pyrimidin-5-yl trifluoromethanesulfonateYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
4 °C

Procedure

Triflic anhydride (13.9 g, 85 mmol) in dry DCM (70 mL) was added slowly to an ice-cold solution of 2-(trifluoromethyl)pyrimidin-5-ol (13.9, 85 mmol) (U.S. Pat. No. 4,558,039), DIPEA (16 mL, 93 mmol) and dry DCM (260 mL) at such a rate that the temperature was kept between 4° C. and 6° C. After the addition was complete, the solution was stirred for 2.5 h at 4° C. and then allowed to warm to RT. Water (50 mL) and 1M phosphoric acid (4.5 mL) were added and the phases were washed and separated. The organic phase was washed successively with water and saturated sodium bicarbonate, dried, filtered and carefully concentrated by rotary evaporation (pressure 300-400 mbar). The dark-red oil was purified by column chromatography with EtOAc-heptanes (1:8 through 1:4) as eluent to give 22.5 g (90%) of the title product as a colourless oil that crystallised in the cold. Alternatively, the product could be purified by distillation, b.p. 75-77° C./10 mbar.

Workup

  1. customwas kept between 4° C. and 6° C
  2. additionAfter the addition
  3. temperatureto warm to RT
  4. washthe phases were washed
  5. customseparated
  6. washThe organic phase was washed successively with water and saturated sodium bicarbonate
  7. customdried
  8. filtrationfiltered
  9. concentrationcarefully concentrated by rotary evaporation (pressure 300-400 mbar)
  10. customThe dark-red oil was purified by column chromatography with EtOAc-heptanes (1:8 through 1:4) as eluent

Sources & evidence

ORD record
ord-e7764099b4474ccc8b257b799414b4ef
Source dataset
uspto-grants-2010_04
Patent number
US07700604B2

Reaction notes

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