Hydrochloric Acid → HCID 22610942, compound

HRID 843564Notes

Reaction equation

HRID 843564 reaction equation
[OH:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([F:9])=[C:4]([N:10]2[C:15](=[O:16])[CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[N:12]([CH3:21])[C:11]2=[O:22])[N:3]=1.[Cl:23][C:24]1[C:29]([OH:30])=[CH:28][C:27]([F:31])=[C:26]([N:32]2[C:37](=[O:38])[CH:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[N:34]([CH3:43])[C:33]2=[O:44])[N:25]=1.C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1.[CH2:69](Br)[C:70]#[CH:71].Cl>C(#N)C>[CH2:28]([O:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([F:9])=[C:4]([N:10]2[C:15](=[O:16])[CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[N:12]([CH3:21])[C:11]2=[O:22])[N:3]=1)[C:27]#[CH:26].[Cl:23][C:24]1[C:29]([O:30][CH2:71][C:70]#[CH:69])=[CH:28][C:27]([F:31])=[C:26]([N:32]2[C:37](=[O:38])[CH:36]=[C:35]([C:39]([F:42])([F:40])[F:41])[N:34]([CH3:43])[C:33]2=[O:44])[N:25]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 7842Propargyl bromideHCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 22610932HCID 22610932, compoundHCID 178480552HCID 178480552, compound

Product 2

HCID 22610942HCID 22610942, compoundHCID 22610943HCID 22610943, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of 10.2 g of a mixture of 1-(2-hydroxy-3-chloro-5-fluoropyridine-6-yl)-3-methyl-4-trifluoromethylpyrimidine-2,6-dione and 1-(2-chloro-3-hydroxy-5-fluoropyridine-6-yl)-3-methyl-4-trifluoromethylpyrimidine-2,6-dione (Example H5), 7.5 g of potassium carbonate and 0.08 g of 18-crown-6 in 180 ml of acetonitrile is treated dropwise with 4.5 ml of propargyl bromide and subsequently heated overnight at 65° C. The mixture is then concentrated by evaporation in vacuo, the residue obtained is treated with ethyl acetate/ice-water mixture and 1 N hydrochloric acid until the pH is 7, the aqueous phase is separated off and extracted with ethyl acetate, and the combined organic phases are washed with water, dried over sodium sulfate and filtered, and the filtrate is concentrated by evaporation. The residue is purified by means of silica gel chromatography (eluent: n-hexane/ethyl acetate 8/2). This gives the desired isomers 1-(2-propargyloxy-3-chloro-5-fluoropyridine-6-yl)-3-methyl-4-trifluoromethylpyrimidine-2,6-dione, m.p. 121-122° C. (compd.no.1.022), 1-(2-chloro-3-propargyloxy-5-fluoropyridine-6-yl)-3-methyl-4-trifluoromethyl-pyrimidine-2,6-dione, m.p, 69-71° C. and 1-(1-propargyloxy-3-chloro-5-fluoro-2-pyridon-6-yl)-3-methyl-4-trifluoromethylpyrimidine-2,6-dione, m.p. 223-224° C.

Workup

  1. concentrationThe mixture is then concentrated by evaporation in vacuo
  2. customthe residue obtained
  3. customthe aqueous phase is separated off
  4. extractionextracted with ethyl acetate
  5. washthe combined organic phases are washed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate is concentrated by evaporation
  9. customThe residue is purified by means of silica gel chromatography (eluent: n-hexane/ethyl acetate 8/2)

Sources & evidence

ORD record
ord-17364e50aac04a4ca2186b30275133a4
Source dataset
uspto-grants-2002_04
Patent number
US06380134B1

Reaction notes

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