Tributylvinyltin → HCID 67171996, compound

HRID 1506457Notes

Reaction equation

HRID 1506457 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:32](=[CH:33][CH:34]=1)[C:13]1=[N:14][O:15][C:16]([C:17]3[C:21]([C:22]([F:25])([F:24])[F:23])=[C:20]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[O:19][N:18]=3)=[C:12]1[CH2:11][C:10]2([F:36])[F:35])(=O)=O.[Cl-].[Li+].[CH2:41]([Sn](CCCC)(CCCC)C=C)[CH2:42]CC>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>[F:35][C:10]1([F:36])[C:9]2[C:32](=[CH:33][CH:34]=[C:7]([CH:41]=[CH2:42])[CH:8]=2)[C:13]2=[N:14][O:15][C:16]([C:17]3[C:21]([C:22]([F:25])([F:23])[F:24])=[C:20]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[O:19][N:18]=3)=[C:12]2[CH2:11]1

Participants

6

Reactant 3

HCID 81998TributylvinyltinHCID 433294Lithium ChlorideHCID 86669914HCID 86669914, compound

Product 1

HCID 67171996HCID 67171996, compoundYield 64.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5,5-difluoro-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl trifluoromethanesulfonate (Preparation 66E, 0.024 g, 0.042 mmol) and lithium chloride (2.60 μL, 0.127 mmol) in dioxane (5.0 mL) was degassed with nitrogen for 15 minutes. To the reaction mixture was added tributyl(vinyl)stannane (0.015 g, 0.047 mmol) followed by tetrakis(triphenylphosphine)palladium(0) (4.90 mg, 4.24 μmol) at room temperature. The resulting reaction mixture was heated at 100° C. overnight. The reaction mixture was cooled to room temperature and filtered. The brownish residue was washed with ethyl acetate (3×10 mL), and the combined filtrates were concentrated in vacuo. The residue was chromatographed using reverse-phase preparative HPLC (Column: LUNA 5 u C18, 21×100 mm:Solvent MeOH(B)—H2O(A), 0.1% TFA: 0% B-100% B, Gradient Time 12 min, Stop Time 20 min, Flow Rate 20 ml/min, Wavelength 220 nM) to yield 5,5-difluoro-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole (0.012 g, 0.027 mmol, 63.7% yield) as a tan viscous liquid. The product had an HPLC ret. time=3.77 min. (condition B). LC/MS M+1=444.20. 1H NMR (500 MHz, CD3OD) δ ppm 7.75 (1H, d, J=7.93 Hz), 7.55-7.68 (2H, m), 7.38-7.57 (4H, m), 7.18-7.38 (1H, m), 6.63 (1H, dd, J=17.70, 10.99 Hz), 5.75 (1H, d, J=17.70 Hz), 5.19 (1H, d, J=10.99 Hz), and 2.85-3.02 (2H, m).

Workup

  1. customwas degassed with nitrogen for 15 minutes
  2. customThe resulting reaction mixture
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered
  5. washThe brownish residue was washed with ethyl acetate (3×10 mL)
  6. concentrationthe combined filtrates were concentrated in vacuo
  7. customThe residue was chromatographed
  8. customreverse-phase preparative HPLC (Column: LUNA 5 u C18, 21×100 mm:Solvent MeOH(B)—H2O(A), 0.1% TFA: 0% B-100% B, Gradient Time 12 min, Stop Time 20 min, Flow Rate 20 ml/min, Wavelength 220 nM)

Sources & evidence

ORD record
ord-c246fe24ebf64011a4c1c731b110587d
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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