Citric Acid → HCID 178469857, compound

HRID 917602Notes

Reaction equation

HRID 917602 reaction equation
CS([C:4]1[N:9]=[C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([Cl:20])[CH:13]=2)[C:7]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:6][N:5]=1)=O.[OH-].[Na+].CN(C)C(=[O:32])C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.O>[OH:32][C:4]1[N:9]=[C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([Cl:20])[CH:13]=2)[C:7]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:6][N:5]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 31374Dimethylacetamide2×HCID 22665570Ethyl 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylsulfinyl)pyrimidine-5-carboxylate

Product 1

HCID 178469857HCID 178469857, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of a whole amount of 2-methylsulfinyl-4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonylpyrimidine (prepared in Example 68-(1)) in tetrahydrofuran 6 ml is dropped 2N aqueous sodium hydroxide solution 1.32 ml under ice cooling over a 2 minite period and the reaction mixture is stirred at the same temperature for 30 minutes. Further tetrahydrofuran 8 ml and N,N-dimethylacetamide 6 ml are added thereto and the mixture is stirred under ice cooling for 30 minites. Thereto are added water 5 ml and N,N-dimethylacetamide 2 ml and the mixture is stirred under ice cooling for one hour. The reaction mixture is acidified with an aqueous 10% citric acid solution and diluted with water, extracted twice with ethyl acetate. The combined organic layer is washed with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is separated by silica gel chromatography (silica gel 20 g, solvent; chloroform:ethyl acetate=5:1→chloroform:isopropanol=30:1) to give 2-hydroxy-4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonylpyrimidine as a slightly yellowish crystalline powder, 618 mg. mp 195-197° C.

Workup

  1. stirringthe mixture is stirred under ice cooling for 30 minites
  2. stirringthe mixture is stirred under ice cooling for one hour
  3. extractionextracted twice with ethyl acetate
  4. washThe combined organic layer is washed with water
  5. dry with materialan aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue is separated by silica gel chromatography (silica gel 20 g, solvent; chloroform:ethyl acetate=5:1→chloroform:isopropanol=30:1)

Sources & evidence

ORD record
ord-1018b22695b4435e936b155909509e76
Source dataset
uspto-grants-2007_09
Patent number
US07273868B2

Reaction notes

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