2-Cyclopentene-1-ol → 3-(3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)cyclopentanone

HRID 1506534Notes

Reaction equation

HRID 1506534 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:27](=[CH:28][CH:29]=1)[C:8]1=[N:9][O:10][C:11]([C:12]3[C:16]([C:17]([F:20])([F:19])[F:18])=[C:15]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[O:14][N:13]=3)=[C:7]1[CH2:6][CH2:5]2.C([O-])(=O)C.[K+].[CH:35]1([OH:40])[CH2:39][CH2:38][CH:37]=[CH:36]1>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[C:21]1([C:15]2[O:14][N:13]=[C:12]([C:11]3[O:10][N:9]=[C:8]4[C:27]5[C:4]([CH2:5][CH2:6][C:7]=34)=[CH:3][C:2]([CH:37]3[CH2:38][CH2:39][C:35](=[O:40])[CH2:36]3)=[CH:29][CH:28]=5)[C:16]=2[C:17]([F:19])([F:20])[F:18])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 3

HCID 2201642-Cyclopentene-1-olHCID 517044Potassium AcetateHCID 671714697-Iodo-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole

Product 1

HCID 671723633-(3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)cyclopentanoneYield 68%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of 7-iodo-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole (Preparation 121B, 370 mg, 0.728 mmol), tetrabutylammonium chloride (202 mg, 0.728 mmol), potassium acetate (214 mg, 2.184 mmol), and anhydrous DMF (2 mL) was bubbled with nitrogen for 3 min. before palladium (II) acetate (16.34 mg, 0.073 mmol) and cyclopent-2-enol (122 mg, 1.456 mmol) were added. The mixture was bubbled for 2 min. and sealed in a 2-dram vial. The mixture was stirred at 75° C. for 3 h. The mixture was cooled, diluted with water (30 ml) and extracted with ethyl acetate (3×10 mL). The combined ethyl acetate extracts were dried (sodium sulfate) and concentrated under reduced pressure. Flash chromatography purification (silica gel column, 5→50% ethyl acetate in n-heptane) afforded 3-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)cyclopentanone (230 mg, 0.495 mmol, 68.0% yield). The compound had an HPLC retention time=4.04 min. (condition C); LC/MS M+1=465.2.

Workup

  1. additionwere added
  2. customThe mixture was bubbled for 2 min.
  3. customsealed in a 2-dram vial
  4. temperatureThe mixture was cooled
  5. additiondiluted with water (30 ml)
  6. extractionextracted with ethyl acetate (3×10 mL)
  7. dry with materialThe combined ethyl acetate extracts were dried (sodium sulfate)
  8. concentrationconcentrated under reduced pressure
  9. customFlash chromatography purification (silica gel column, 5→50% ethyl acetate in n-heptane)

Sources & evidence

ORD record
ord-129bbe7466f5417ba8ececaa29e3c2e9
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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