Water → 3-[7-fluoro-2,3-dihydro-4-(2-propynyl)-1,4-benzoxazin-3-on-6-yl]-1-methyl-6-trifluoromethyl-2(1H)-pyridone

HRID 1385932Notes

Reaction equation

HRID 1385932 reaction equation
[F:1][C:2]1[C:12]([C:13]2[C:14](=[O:24])[N:15]([CH3:23])[C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=2)=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1.[H-].[Na+].[CH2:27](Br)[C:28]#[CH:29].O>CN(C=O)C>[F:1][C:2]1[C:12]([C:13]2[C:14](=[O:24])[N:15]([CH3:23])[C:16]([C:19]([F:20])([F:21])[F:22])=[CH:17][CH:18]=2)=[CH:11][C:5]2[N:6]([CH2:29][C:28]#[CH:27])[C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 184083243-(7-fluoro-2,3-dihydro-1,4-benzoxazin-3-on-6-yl)-1-methyl-6-trifluoromethyl-2(1H)-pyridone

Product 1

HCID 184083193-[7-fluoro-2,3-dihydro-4-(2-propynyl)-1,4-benzoxazin-3-on-6-yl]-1-methyl-6-trifluoromethyl-2(1H)-pyridoneYield 72.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.3 g (0.87 mmol) of 3-(7-fluoro-2,3-dihydro-1,4-benzoxazin-3-on-6-yl)-1-methyl-6-trifluoromethyl-2(1H)-pyridone was dissolved in 1 ml of DMF, and 0.04 g (1 mmol) of 60% sodium hydride was added under cooling with ice, followed by stirring at room temperature for 15 minutes. Then, 0.12 g (1 mmol) of propargyl bromide was added thereto. The mixture was stirred at room temperature for 3 hours, then poured into water and extracted with ethyl acetate. After washing with water, the organic layer was dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and then, the obtained residue was purified by silica gel column chromatography to obtain 0.24 g (yield: 72%) of the desired product. Melting point: 166-168° C. 1H-NMR (400 MHz, CDCl3) δ value: 2.24(1H,t), 3.68(3H,s), 4.63(2H,s), 4.68(2H,d), 6.76(1H,d), 6.83(1H,d), 7.40(1H,d), 7.51(1H,d)ppm.

Workup

  1. temperatureunder cooling with ice
  2. stirringThe mixture was stirred at room temperature for 3 hours
  3. extractionextracted with ethyl acetate
  4. washAfter washing with water
  5. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  6. distillationEthyl acetate was distilled off under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-81287728de244c849e2e52d9a0ddb00f
Source dataset
uspto-grants-2001_07
Patent number
US06265349B1

Reaction notes

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