Ethyl Acetate → 3-(5-chloro-3,4-dihydro-7-fluoro-2H-1-benzopyran-8-yl)-6-trifluoromethyluracil

HRID 440690Notes

Reaction equation

HRID 440690 reaction equation
[Cl:1][C:2]1[C:7]2[CH2:8][CH2:9][CH2:10][O:11][C:6]=2[C:5]([N:12]=[C:13]=[O:14])=[C:4]([F:15])[CH:3]=1.[NH2:16]/[C:17](/[C:24]([F:27])([F:26])[F:25])=[CH:18]\[C:19](OCC)=[O:20].[H-].[Na+].C(OCC)(=O)C>O1CCCC1.CCCCCC>[Cl:1][C:2]1[C:7]2[CH2:8][CH2:9][CH2:10][O:11][C:6]=2[C:5]([N:12]2[C:19](=[O:20])[CH:18]=[C:17]([C:24]([F:27])([F:26])[F:25])[NH:16][C:13]2=[O:14])=[C:4]([F:15])[CH:3]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 5702529Ethyl 3-amino-4,4,4-trifluorocrotonateHCID 224047285-chloro-3,4-dihydro-7-fluoro-2H-1-benzopyran-8-yl isocyanate

Product 1

HCID 224048003-(5-chloro-3,4-dihydro-7-fluoro-2H-1-benzopyran-8-yl)-6-trifluoromethyluracil

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

By a method analogous to that of Example 1, Step G, 2.5 grams (0.011 mole) of 5-chloro-3,4-dihydro-7-fluoro-2H-1-benzopyran-8-yl isocyanate was reacted with ethyl 3-amino-4,4,4-trifluorocrotonate and 0.66 gram (0.012 mole) of sodium hydride (60% in mineral oil) in 150 mL of tetrahydrofuran. The crude reaction product was subjected to column chromatography on silica gel, with 1:2 ethyl acetate:hexane as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 3.0 grams of 3-(5-chloro-3,4-dihydro-7-fluoro-2H-1-benzopyran-8-yl)-6-trifluoromethyluracil. The NMR spectrum was consistent with the proposed structure.

Workup

  1. customThe crude reaction product
  2. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c72d9c88583f4d8fb00bdd567fcfeee9
Source dataset
uspto-grants-1996_05
Patent number
US05521147

Reaction notes

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