4-Chloro-2-fluoro-5-isopropoxyphenyl isocyanate → HCID 20025954, compound

HRID 1722939Notes

Reaction equation

HRID 1722939 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:6][C:5]([N:12]=[C:13]=[O:14])=[C:4]([F:15])[CH:3]=1.[NH2:16]/[C:17](/[CH3:25])=[C:18](/[F:24])\[C:19](OCC)=[O:20]>C(OCC)C>[Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:10])[CH3:11])=[CH:6][C:5]([N:12]2[C:19](=[O:20])[C:18]([F:24])=[C:17]([CH3:25])[NH:16][C:13]2=[O:14])=[C:4]([F:15])[CH:3]=1

Participants

4

Reactant 2

HCID 132729244-Chloro-2-fluoro-5-isopropoxyphenyl isocyanateHCID 55288618HCID 55288618, compound

Product 1

HCID 20025954HCID 20025954, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of 6.00 g of 4-chloro-2-fluoro-5-isopropoxyphenyl isocyanate in 100 ml of absolute diethyl ether is added dropwise while stirring at room temperature during 1 hour to a solution of 4.00 g of ethyl 3-amino-2-fluorocrotonate and the reaction mixture is stirred for 16 hours. The mixture is then evaporated to dryness under reduced pressure, the residue is dissolved in 50 ml of absolute dimethylformamide and the solution is added while stirring at room temperature to a solution of 1.31 g of a 55% sodium hydride dispersion in 50 ml of dimethylformamide and 100 ml of isopropyl alcohol. The mixture is subsequently stirred at room temperature for 4 hours, adjusted to pH ~4 with concentrated acetic acid and concentrated under reduced pressure. The residue is poured into 1 l of water and extracted twice with 200 ml of ethyl acetate each time, and the organic phases are washed with water, dried over anhydrous sodium sulphate and evaporated to dryness under reduced pressure. The residue is purified by chromatography on a silica gel column using ethyl acetate/n-hexane as the eluent and subsequently recrystallized from ethyl acetate/diethyl ether. There is obtained 3-(4-chloro-2-fluoro-5-isopropoxyphenyl)-5 -fluoro-6-methyl-2,4(1H,3H)-pyrimidinedione, m.p. 162°-164° C.

Workup

  1. customThe mixture is then evaporated to dryness under reduced pressure
  2. dissolutionthe residue is dissolved in 50 ml of absolute dimethylformamide
  3. additionthe solution is added
  4. stirringwhile stirring at room temperature to a solution of 1.31 g of a 55% sodium hydride dispersion in 50 ml of dimethylformamide
  5. stirringThe mixture is subsequently stirred at room temperature for 4 hours
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue is poured into 1 l of water
  8. extractionextracted twice with 200 ml of ethyl acetate each time
  9. washthe organic phases are washed with water
  10. dry with materialdried over anhydrous sodium sulphate
  11. customevaporated to dryness under reduced pressure
  12. customThe residue is purified by chromatography on a silica gel column
  13. customsubsequently recrystallized from ethyl acetate/diethyl ether

Sources & evidence

ORD record
ord-a8b86d7744224c0e8aa03b34e7377ebe
Source dataset
uspto-grants-1989_08
Patent number
US04859229

Reaction notes

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