Tetramethylammonium fluoride → 6-[2-(2-Chloro-5-methoxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-4-methyl-4H-benzo[1,4]oxazin-3-one

HRID 2386695Notes

Reaction equation

HRID 2386695 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[CH:10]([CH3:25])[C:11]([C:13]1[CH:14]=[CH:15][C:16]2[O:21][CH2:20][C:19](=[O:22])[N:18]([CH3:23])[C:17]=2[CH:24]=1)=[O:12].[F:26][C:27]([Si](C)(C)C)([F:29])[F:28].[F-].C[N+](C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[CH:10]([CH3:25])[C:11]([C:13]1[CH:14]=[CH:15][C:16]2[O:21][CH2:20][C:19](=[O:22])[N:18]([CH3:23])[C:17]=2[CH:24]=1)([OH:12])[C:27]([F:29])([F:28])[F:26]

Participants

6

Reactant 4

HCID 67803Tetramethylammonium fluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 66697202HCID 66697202, compound

Product 1

HCID 666971746-[2-(2-Chloro-5-methoxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-4-methyl-4H-benzo[1,4]oxazin-3-oneYield 78.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 6-[2-(2-chloro-5-methoxy-phenyl)-propionyl]-4-methyl-4H-benzo[1,4]oxazin-3-one (1.17 g) in tetrahydrofuran (60 ml) was added a solution of (trifluoromethyl)trimethylsilane (703 mg) in tetrahydrofuran (10 ml) at 0° C. Tetramethylammonium fluoride (30 mg) was added and the mixture was stirred at 0° C. for 30 min and at room temperature for 15 min. A 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (3.26 ml) was added and the mixture was stirred for 20 min. The solvent was evaporated and the residue was dissolved in dichloromethane. The organic phase was washed with water, dried (MgSO4), filtered and concentrated. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>7:3) to give the title compound (1.1 g) as a colorless solid. MS (m/e, ISP neg. ion)=428.4 [M−H+].

Workup

  1. stirringthe mixture was stirred for 20 min
  2. customThe solvent was evaporated
  3. dissolutionthe residue was dissolved in dichloromethane
  4. washThe organic phase was washed with water
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>7:3)

Sources & evidence

ORD record
ord-7479d0f9c9dc42f4bae5b359316d53a2
Source dataset
uspto-grants-2012_09
Patent number
US08268820B2

Reaction notes

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