Tributylvinyltin → 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-7-vinyl-4H-chromeno[4,3-c]isoxazole

HRID 1506441Notes

Reaction equation

HRID 1506441 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:11]3=[N:12][O:13][C:14]([C:15]4[C:19]([C:20]([F:23])([F:22])[F:21])=[C:18]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[O:17][N:16]=4)=[C:10]3[CH2:9][O:8][C:6]=2[CH:7]=1.[CH2:30]([Sn](CCCC)(CCCC)C=C)[CH2:31]CC.[Cl-].[Li+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:24]1([C:18]2[O:17][N:16]=[C:15]([C:14]3[O:13][N:12]=[C:11]4[C:5]5[CH:4]=[CH:3][C:2]([CH:30]=[CH2:31])=[CH:7][C:6]=5[O:8][CH2:9][C:10]=34)[C:19]=2[C:20]([F:22])([F:21])[F:23])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 81998TributylvinyltinHCID 433294Lithium ChlorideHCID 671687467-bromo-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4H-chromeno[4,3-c]isoxazole

Product 1

HCID 671678993-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-7-vinyl-4H-chromeno[4,3-c]isoxazoleYield 67%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a heterogeneous solution of 7-bromo-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4H-chromeno[4,3-c]isoxazole (Preparation 62F, 0.105 g, 0.227 mmol) in dioxane (2.0 mL) in a sealed tube was added sequentially tributyl(vinyl)stannane (0.073 mL, 0.249 mmol) and lithium chloride (0.029 g, 0.680 mmol). The mixture was degassed under reduced pressure and charged with nitrogen (3×). To the mixture was added tetrakis(triphenylphosphine)palladium(0) (0.026 g, 0.023 mmol), and the mixture was stirred under a strong stream of nitrogen for 5 min. The reaction mixture was sealed, immersed in an oil bath at 100° C., and stirred overnight. As it reached 100° C., the solution became near homogeneous. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with dichloromethane (10 mL), filtered through a pad of Celite, and rinsed with dichloromethane (10 mL). The filtrate was concentrated, and the residue was purified by flash silica gel chromatography using a 5% mixture of ethyl acetate in hexane to give 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-7-vinyl-4H-chromeno[4,3-c]isoxazole (0.062 g, 0.151 mmol, 67% yield) as a white solid. The product had an HPLC ret. time=3.84 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=411.0.

Workup

  1. customThe mixture was degassed under reduced pressure
  2. additioncharged with nitrogen (3×)
  3. customThe reaction mixture was sealed
  4. customimmersed in an oil bath at 100° C.
  5. stirringstirred overnight
  6. customreached 100° C.
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. additionthe residue was diluted with dichloromethane (10 mL)
  9. filtrationfiltered through a pad of Celite
  10. washrinsed with dichloromethane (10 mL)
  11. concentrationThe filtrate was concentrated
  12. customthe residue was purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-08d1e3afcbe242b394ebfe54904635de
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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