Bromine → HCID 86723840, compound

HRID 576741Notes

Reaction equation

HRID 576741 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[C:5]([N:9]2[CH2:14][CH2:13][C:12](=[O:15])[NH:11][C:10]2=[O:16])[CH:6]=[CH:7][CH:8]=1.BrBr.S([O-])([O-])(=O)=S.[Na+].[Na+].[Br:28][C:29]1[C:30](=[O:46])[NH:31][C:32](=[O:45])[N:33]([C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:44])([F:43])[F:42])[CH:36]=2)[CH:34]=1.BrC1(Br)CN(C2C=CC=C(C(F)(F)F)C=2)C(=O)NC1=O.BrC1CN(C2C=CC=C(C(F)(F)F)C=2)C(=O)NC1=O.[Cl-].[Li+]>C(O)(=O)C.CN(C)C=O.O>[Br:28][C:29]1[C:30](=[O:46])[NH:31][C:32](=[O:45])[N:33]([C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:44])([F:43])[F:42])[CH:36]=2)[CH:34]=1.[F:18][C:2]([F:1])([F:17])[C:3]1[CH:4]=[C:5]([N:9]2[CH:14]=[CH:13][C:12](=[O:15])[NH:11][C:10]2=[O:16])[CH:6]=[CH:7][CH:8]=1

Participants

12

Reactant 7

HCID 24408BromineHCID 24477Sodium ThiosulfateHCID 433294Lithium ChlorideHCID 70692250HCID 70692250, compoundHCID 86723840HCID 86723840, compoundHCID 86723842HCID 86723842, compoundHCID 86723843HCID 86723843, compound

Product 2

HCID 86723840HCID 86723840, compoundHCID 86723841HCID 86723841, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(3-trifluoromethylphenyl)dihydropyrimidin-2,4(1H,3H)-dione (prepared in Reference Example 96) (770.0 mg) in acetic acid (10.0 ml) was added bromine (0.18 ml) and the resulting mixture was stirred with heating under reflux for two hours. To the reaction mixture were added water (30 ml) and 10% aqueous sodium thiosulfate solution (5 ml) and the precipitated solids were collected by filtration with water to afford a mixture containing 5-bromo-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione, 5,5-dibromo-1-(3-trifluoromethylphenyl)dihydropyrimidin-2,4(1H,3H)-dione and 5-bromo-1-(3-trifluoromethylphenyl)dihydropyrimidin-2,4(1H,3H)-dione (800.0 mg). A solution of the resulting mixture (800.0 mg) and lithium chloride (122.3 mg) in N,N-dimethyl formamide (5.0 ml) was stirred at 120° C. for one and a half hours. To the reaction mixture was added water (20 ml) and the resulting mixture was extracted with ethyl acetate (20 ml×2), and the organic layer was washed with water (20 ml×2) and saturated saline (20 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford 5-bromo-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione (473.1 mg) and 1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione (135.8 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for two hours
  3. filtrationthe precipitated solids were collected by filtration with water
  4. customto afford a mixture
  5. extractionthe resulting mixture was extracted with ethyl acetate (20 ml×2)
  6. washthe organic layer was washed with water (20 ml×2) and saturated saline (20 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-7ca61d9bd7a843c98a1ea492b47c803d
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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