Trifluoroacetic acid → 1-(5-Fluoro-2-pyrimidinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylic acid

HRID 2081047Notes

Reaction equation

HRID 2081047 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:12][CH:11]([C:13]([O:15]C(C)(C)C)=[O:14])[N:10]([CH3:20])[C:9]2=[O:21])=[N:6][CH:7]=1.FC(F)(F)C(O)=O>ClCCl>[F:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:12][CH:11]([C:13]([OH:15])=[O:14])[N:10]([CH3:20])[C:9]2=[O:21])=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 671031911,1-Dimethylethyl 1-(5-fluoro-2-pyrimidinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 671036301-(5-Fluoro-2-pyrimidinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylic acidYield 112.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (300 mg, 1.498 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-chloro-5-fluoropyrimidine (0.194 ml, 1.573 mmol) in 1,4-dioxane (10 ml) was treated with cesium carbonate (732 mg, 2.247 mmol), Xantphos™ (65.0 mg, 0.112 mmol), and tris(dibenzylideneacetone)dipalladium(0) (34.3 mg, 0.037 mmol) and then heated at reflux for ˜3 hrs. The mixture was cooled to room temperature, diluted with water (˜25 ml) and extracted with ethyl acetate (3×). The combined ethyl acetate layers were washed with water and then with brine and evaporated to give a yellow/brown residue. This was purified by automated silica-gel column chromatography (Biotage SP-4), eluting with a 0-100% gradient of ethyl acetate in isohexane (8 column volumes), to give 1,1-dimethylethyl 1-(5-fluoro-2-pyrimidinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylate (232 mg, 52.3% yield) as a white solid. (ii) 1,1-Dimethylethyl 1-(5-fluoro-2-pyrimidinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylate (232 mg, 0.783 mmol) was dissolved in a mixture of trifluoroacetic acid (2 ml, 26.0 mmol) and dichloromethane (4 ml) at 0° C. and then left to warm to room temperature and stirred overnight. The mixture was evaporated (azeotroping with toluene and then with dichloromethane to remove all TFA traces) to give 1-(5-fluoro-2-pyrimidinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylic acid (211 mg) as a white solid which was used without further purification in subsequent chemistry. LC/MS MH+=240.85.

Workup

  1. waitleft
  2. customThe mixture was evaporated (
  3. customazeotroping with toluene
  4. customwith dichloromethane to remove all TFA

Sources & evidence

ORD record
ord-5391f0242fe54fc79999093f21b88de8
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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