Sodium hydride → 1-Amino-3-(4-chloro-2-fluoro-5-isopropyloxyphenyl)-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione

HRID 380314

Reaction equation

HRID 380314 reaction equation
[H-].[Na+].[NH2:3]/[C:4](/[C:11]([F:14])([F:13])[F:12])=[CH:5]\[C:6](OCC)=[O:7].[Cl:15][C:16]1[C:21]([O:22][CH:23]([CH3:25])[CH3:24])=[CH:20][C:19]([N:26]=[C:27]=[O:28])=[C:18]([F:29])[CH:17]=1.[N+:30](C1C=C([N+]([O-])=O)C=CC=1ON)([O-])=O>CN(C)C=O.C1(C)C=CC=CC=1>[NH2:30][N:3]1[C:4]([C:11]([F:14])([F:13])[F:12])=[CH:5][C:6](=[O:7])[N:26]([C:19]2[CH:20]=[C:21]([O:22][CH:23]([CH3:24])[CH3:25])[C:16]([Cl:15])=[CH:17][C:18]=2[F:29])[C:27]1=[O:28]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 87140O-(2,4-dinitrophenyl)hydroxylamineHCID 5702529Ethyl 3-amino-4,4,4-trifluorocrotonateHCID 132729244-Chloro-2-fluoro-5-isopropoxyphenyl isocyanate

Product 1

HCID 184029211-Amino-3-(4-chloro-2-fluoro-5-isopropyloxyphenyl)-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent3×

Procedure

A suspension of sodium hydride (10 g, 60% in oil) in N,N-dimethylformamide (30 ml) was stirred at 0° C. under nitrogen while a solution of ethyl 3-amino-4,4,4-trifluorocrotonate (4.5 g) in N,N-dimethylformamide (20 ml) was added dropwise. After stirring for 15 minutes, a solution of 4-chloro-2-fluoro-5-isopropyloxyphenylisocyanate (5.6 g) in toluene (25 ml) was added slowly at -35° C. The solution was stirred at room temperature for 2 hours and treated with a solution of 2,4-dinitrophenoxyamine (5.8 g) in N,N-dimethylformamide (20 ml). Stirring was continued for 3 days. The solution was processed and gave a solid which was chromatographed on silica gel eluting with ethyl acetate:hexane, 1:5, containing 0.1% of triethylamine. 1-Amino-3-(4-chloro-2-fluoro-5-isopropyloxyphenyl)-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione was obtained as a white solid (5.3 g).

Workup

  1. additionwas added dropwise
  2. stirringThe solution was stirred at room temperature for 2 hours
  3. stirringStirring
  4. waitwas continued for 3 days
  5. customgave a solid which
  6. customwas chromatographed on silica gel eluting with ethyl acetate
  7. additionhexane, 1:5, containing 0.1% of triethylamine

Sources & evidence

ORD record
ord-9dde30c115a04f4482d299623e77fb0e
Source dataset
uspto-grants-2001_10
Patent number
US06303543B1

Linked notes

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