Sodium Chloride → 4-[(1R,2R)-2-benzyloxy-1-methyl-propoxy]-2-chloro-5-(trifluoromethyl)pyrimidine

HRID 2199514Notes

Reaction equation

HRID 2199514 reaction equation
[CH2:1]([O:8][C@H:9]([CH3:21])[C@@H:10]([CH3:20])[O:11][C:12]1[C:17](I)=[CH:16][N:15]=[C:14]([Cl:19])[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F-].[K+].[F:24][C:25]([Si](C)(C)C)([F:27])[F:26].[Cl-].[Na+]>CN1C(=O)CCC1.C1COCC1.[Cu]I>[CH2:1]([O:8][C@H:9]([CH3:21])[C@@H:10]([CH3:20])[O:11][C:12]1[C:17]([C:25]([F:27])([F:26])[F:24])=[CH:16][N:15]=[C:14]([Cl:19])[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 522689Potassium FluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 584679604-((1R,2R)-2-benzyloxy-1-methylpropoxy)-2-chloro-5-iodopyrimidine

Product 1

HCID 468994684-[(1R,2R)-2-benzyloxy-1-methyl-propoxy]-2-chloro-5-(trifluoromethyl)pyrimidineYield 54%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-((1R,2R)-2-benzyloxy-1-methylpropoxy)-2-chloro-5-iodopyrimidine in NMP and THF was admixed at room temperature with stirring with copper(I) iodide, potassium fluoride and (trifluoromethyl)trimethylsilane. The mixture was stirred for 5.5 hours at 80° C. After cooling, the mixture was added to dilute sodium chloride solution and extracted with acetic ester (2×). The combined organic phases were dried (Na2SO4), filtered and concentrated by evaporation. The residue obtained was purified by means of chromatography (hexane/acetic ester 4:1) (yield: 54%).

Workup

  1. customwas admixed at room temperature
  2. temperatureAfter cooling
  3. extractionextracted with acetic ester (2×)
  4. dry with materialThe combined organic phases were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated by evaporation
  7. customThe residue obtained
  8. customwas purified by means of chromatography (hexane/acetic ester 4:1) (yield: 54%)

Sources & evidence

ORD record
ord-3f0b5c7982d549fb97715e1c41dfef22
Source dataset
uspto-grants-2016_06
Patent number
US09359306B2

Reaction notes

Loading…