Tetrahydrofuran → 2-(2,2-Diethoxyethoxy)-5-fluoropyrimidine

HRID 81629

Reaction equation

HRID 81629 reaction equation
O1CCCC1.[CH2:6]([O:8][CH:9]([O:12][CH2:13][CH3:14])[CH2:10][OH:11])[CH3:7].CN(C)C(=O)C.[Cl:21][C:22]1[N:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=1>O>[CH2:6]([O:8][CH:9]([O:12][CH2:13][CH3:14])[CH2:10][O:11][C:22]1[N:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=1)[CH3:7].[Cl:21][C:22]1[N:27]=[CH:26][C:25]([O:11][CH2:10][CH:9]([O:12][CH2:13][CH3:14])[O:8][CH2:6][CH3:7])=[CH:24][N:23]=1

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 121292,2-DiethoxyethanolHCID 31374DimethylacetamideHCID 5834662-Chloro-5-fluoropyrimidine

Product 2

HCID 684276832-(2,2-Diethoxyethoxy)-5-fluoropyrimidineYield 67%HCID 866458972-Chloro-5-(2,2-diethoxyethoxy)pyrimidineYield 21%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

With cooling with ice, a tetrahydrofuran solution (2 ml) of 2,2-diethoxyethanol (668 mg, 4.98 mmol) was added to a mixed tetrahydrofuran (4 ml)/N,N-dimethylacetamide (2 ml) solution of 2-chloro-5-fluoropyrimidine (600 mg, 4.53 mmol), and stirred under a nitrogen atmosphere for 1 hour. Water was added to the reaction solution, and extracted with ethyl acetate. Next, the organic layer was washed with saturated saline water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Moritex, acetone:hexane=1:25) to obtain 2-(2,2-diethoxyethoxy)-5-fluoropyrimidine (699 mg, yield: 67%) as a colorless oil, and 2-chloro-5-(2,2-diethoxyethoxy)pyrimidine (233 mg, 21%) as a colorless solid.

Workup

  1. temperatureWith cooling with ice
  2. extractionextracted with ethyl acetate
  3. washNext, the organic layer was washed with saturated saline water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (Moritex, acetone:hexane=1:25)

Sources & evidence

ORD record
ord-e27b373c1e6a4e388b8ecb2abf664fe7
Source dataset
uspto-grants-2014_09
Patent number
US08846700B2

Linked notes

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