Dimethylformamide → 7-Methoxy-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)naphtho[1,2-c]isoxazol-5(4H)-one

HRID 1506455Notes

Reaction equation

HRID 1506455 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:28](=[CH:29][CH:30]=1)[C:9]1=[N:10][O:11][C:12]([C:13]3[C:17]([C:18]([F:21])([F:20])[F:19])=[C:16]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[O:15][N:14]=3)=[C:8]1[CH2:7][CH2:6]2.CN(C)C=[O:34].C(OO)(C)(C)C>C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:28](=[CH:29][CH:30]=1)[C:9]1=[N:10][O:11][C:12]([C:13]3[C:17]([C:18]([F:21])([F:19])[F:20])=[C:16]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[O:15][N:14]=3)=[C:8]1[CH2:7][C:6]2=[O:34]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 6410tert-Butyl hydroperoxide3×HCID 671716707-Methoxy-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole

Product 1

HCID 671718177-Methoxy-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)naphtho[1,2-c]isoxazol-5(4H)-oneYield 36%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 7-methoxy-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole (Preparation 66A, 0.103 g, 0.250 mmol) and cuprous iodide (0.476 mg, 0.0025 mmol) in acetonitrile (2.0 mL) at room temperature [note: the reactant was sparingly soluble in acetonitrile, so dimethyl formamide (0.5 ml) was added to solubilize the reactant] was added t-butyl hydroperoxide (0.250 mL, 1.50 mmoL). The reaction mixture was heated at 50° C. overnight. An additional aliquot of t-butyl hydroperoxide (0.250 mL, 1.50 mmol) was added, and the reaction was heated at 50° C. overnight. A small change in the amount of product was noted, so an additional aliquot of t-butyl hydroperoxide (0.250 mL, 1.50 mmol) was added. The reaction mixture was heated at 50° C. overnight. The reaction mixture was concentrated in vacuo, and the crude mixture was chromatographed using reverse-phase preparative HPLC to give the product [39 mg, 0.094 mmol, 36% yield] as a tan solid. The product had an HPLC ret. time=3.90 min. (condition B). LC/MS M+1=427.10.

Workup

  1. customat room temperature
  2. temperaturethe reaction was heated at 50° C. overnight
  3. temperatureThe reaction mixture was heated at 50° C. overnight
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe crude mixture was chromatographed
  6. customto give the product [39 mg, 0.094 mmol, 36% yield] as a tan solid

Sources & evidence

ORD record
ord-5a6400af6f324f4f84d2be2a182a5b89
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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