Water → HCID 66697308, compound

HRID 2096726Notes

Reaction equation

HRID 2096726 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[CH:9]([CH3:28])[C:10]([C:16]1[CH:17]=[CH:18][C:19]2[O:24][CH2:23][C:22](=[O:25])[N:21]([CH3:26])[C:20]=2[CH:27]=1)([OH:15])C(F)(F)F.[F:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][C:37]=1F)[C:33]#[N:34].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:37]2[CH:36]=[CH:35][C:32]([C:33]#[N:34])=[CH:31][C:30]=2[F:29])=[CH:4][C:3]=1[CH:9]([CH3:28])[C:10]([C:16]1[CH:17]=[CH:18][C:19]2[O:24][CH2:23][C:22](=[O:25])[N:21]([CH3:26])[C:20]=2[CH:27]=1)=[O:15]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 5872033,4-DifluorobenzonitrileHCID 666971956-[2-(2-Chloro-5-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-4-methyl-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 66697308HCID 66697308, compoundYield 82.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of 6-[2-(2-chloro-5-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-4-methyl-4H-benzo[1,4]oxazin-3-one (Example 1, step 4, 100 mg) in N,N-dimethylacetamide (1.8 ml) were added 3,4-difluorobenzonitrile (41 mg) and cesium carbonate (235 mg). The mixture was heated under microwave conditions for 30 min to 120° C. After cooling to room temperature, water was added and the mixture was extracted with EtOAc. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>1:1) to give 4-{4-chloro-3-[1-methyl-2-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-2-oxo-ethyl]-phenoxy}-3-fluoro-benzonitrile (92 mg). In analogy to Example 1, step 3, this compound was reacted with trifluoromethyl trimethylsilane and tetramethylammonium fluoride to give the title compound (89 mg) as a colorless solid. MS (m/e)=535.1 [M+H+].

Workup

  1. temperatureThe mixture was heated under microwave conditions for 30 min to 120° C
  2. extractionthe mixture was extracted with EtOAc
  3. dry with materialThe organic phase was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>1:1)

Sources & evidence

ORD record
ord-a28f87b2aefb4bc982d3a06a0e2199ce
Source dataset
uspto-grants-2013_05
Patent number
US08450313B2

Reaction notes

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