Hydrochloric Acid → HCID 69672521, compound

HRID 1426315Notes

Reaction equation

HRID 1426315 reaction equation
[CH:1]([C:4]1[N:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[N:7]=[C:6]([C:14]([O:16]CC)=[O:15])[CH:5]=1)([CH3:3])[CH3:2].CC(C)([O-:22])C.[K+].O=O.S([O-])([O-])=O.[Na+].[Na+].O.[OH-].[Li+].Cl>O1CCCC1.O>[OH:22][C:1]([C:4]1[N:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[N:7]=[C:6]([C:14]([OH:16])=[O:15])[CH:5]=1)([CH3:3])[CH3:2]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 977Oxygen2×HCID 24437Sodium SulfiteHCID 168937Lithium hydroxide, monohydrateHCID 23665647Potassium tert-butoxideHCID 69672674HCID 69672674, compound

Product 1

HCID 69672521HCID 69672521, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-35 °C

Procedure

A solution of ethyl 6-isopropyl-2-(trifluoromethyl)pyrimidine-4-carboxylate (2.00 g, 7.63 mmol, from Step A) in tetrahydrofuran (40 mL) was added to 1.0M potassium tert-butoxide in THF (22.9 mL, 22.9 mmol) held at −40° C. After stirring for 45 minutes at this temperature, oxygen was introduced below the surface of the reaction solution via a syringe attached to a balloon containing oxygen. The oxygen was bubbled subsurface periodically (by addition and removal of an outlet) for 20 minutes, while maintaining the reaction temperature between −40 to −30° C. The reaction was then allowed to slowly reach room temperature with periodic bubbling of oxygen through the solution. Near a temperature of −30 deg C., the reaction turned from purple to orange in color. The reaction was kept under atmosphere of oxygen overnight, at which time the reaction was quenched with water and sodium sulfite (2 g, 20 mmol) was added. Lithium hydroxide, monohydrate (0.928 g, 22.1 mmol) was also added and the reaction was stirred overnight. Concentrated HCl was added drop wise into the reaction to achieve pH between 3 and 4. The layers were separated and the THF layer was reserved for addition to the subsequent two ethyl acetate extractions. The combined extracts were washed with brine, dried over sodium sulfate, filtered and concentrated, then azeotroped twice with MeOH to afford a yellow syrup which was used without further purification (1.7 g, 62%). 1H NMR (400 MHz, CD3OD) δ 8.51 (s, 1H), 1.57 (s, 6H); LCMS (M+H)+: 251.0

Workup

  1. customheld at −40° C
  2. additionwas introduced below the surface of the reaction solution via a syringe
  3. customThe oxygen was bubbled
  4. additionsubsurface periodically (by addition and removal of an outlet) for 20 minutes
  5. customwas then allowed to slowly reach room temperature
  6. customwith periodic bubbling of oxygen through the solution
  7. customNear a temperature of −30 deg C
  8. additionwas added
  9. customwise into the reaction
  10. customThe layers were separated
  11. additionthe THF layer was reserved for addition to the subsequent two ethyl acetate extractions
  12. washThe combined extracts were washed with brine
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customazeotroped twice with MeOH
  17. customto afford a yellow syrup which
  18. customwas used without further purification (1.7 g, 62%)

Sources & evidence

ORD record
ord-f44b2b89467440379464a7d5f7875764
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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