Sulfuric Acid → HCID 18402914, compound

HRID 2270910Notes

Reaction equation

HRID 2270910 reaction equation
[Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12](N)=[CH:11][CH:10]=2)=[CH:6][C:5]([N:16]2[C:21](=[O:22])[CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[NH:18][C:17]2=[O:27])=[C:4]([F:28])[CH:3]=1.S(=O)(=O)(O)[OH:30].N([O-])=O.[Na+].NC(N)=O>O.[Cu-]=O>[Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([OH:30])=[CH:11][CH:10]=2)=[CH:6][C:5]([N:16]2[C:21](=[O:22])[CH:20]=[C:19]([C:23]([F:25])([F:24])[F:26])[NH:18][C:17]2=[O:27])=[C:4]([F:28])[CH:3]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 1176UreaHCID 18403007HCID 18403007, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 18402914HCID 18402914, compound

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 962WaterSolvent3×

Procedure

3-[4-Chloro-2-fluoro-5-(4-aminophenoxy)phenyl]-6-trifluoromethyl-1,2,3,4-tetrahydro-pyrimidine-2,4-dione (2.0 g) was mixed with hot 30% sulfuric acid (5 ml) and ic/water (5.0 g) was added. The mixture kept at 10° C. while a solution of sodium nitrite (0.45 g) in water (5 ml) was slowly introduced at the bottom of the stirred mixture. After stirring for 10 minutes, urea (0.1 g) was added, followed by a solution of copper(2)nitrate (18.0 g) in water (170 ml), and copper(1)oxide (0.7 g). The mixture was stirred for 10 minutes, extracted with diethyl ether (50 ml×3), and dried over sodium sulfate. The crude product was purified by column chromatography (hexane:ethyl acetate, 4:1) to give 3-[4-chloro -2-fluoro-5-(4-hydroxyphenoxy)phenyl]-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (Intermediate 11-31), (1.0 g).

Workup

  1. additionwas slowly introduced at the bottom of the stirred mixture
  2. stirringThe mixture was stirred for 10 minutes
  3. extractionextracted with diethyl ether (50 ml×3)
  4. dry with materialdried over sodium sulfate
  5. customThe crude product was purified by column chromatography (hexane:ethyl acetate, 4:1)

Sources & evidence

ORD record
ord-e6d30d11fd0d42429056776b0377cec0
Source dataset
uspto-grants-2001_12
Patent number
US06333296B1

Reaction notes

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