Tributylvinyltin → HCID 67168124, compound

HRID 1506470Notes

Reaction equation

HRID 1506470 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[C:7](=[C:13]([C:16]4[O:20][N:19]=[C:18]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)[C:17]=4[C:27]([F:30])([F:29])[F:28])[O:14][N:15]=3)[CH2:8][N:9]([CH3:12])[C:10]=2[CH:11]=1.[CH2:31]([Sn](CCCC)(CCCC)C=C)[CH2:32]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>[CH3:12][N:9]1[C:10]2[CH:11]=[C:2]([CH:31]=[CH2:32])[CH:3]=[CH:4][C:5]=2[C:6]2=[N:15][O:14][C:13]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:17]=3[C:27]([F:29])([F:28])[F:30])=[C:7]2[CH2:8]1

Participants

6

Reactant 3

HCID 81998TributylvinyltinHCID 433294Lithium ChlorideHCID 67168450HCID 67168450, compound

Product 1

HCID 67168124HCID 67168124, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a heterogeneous solution of 7-bromo-5-methyl-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydroisoxazolo[4,3-c]quinoline (Preparation 77E, 0.040 g, 0.084 mmol) in dioxane (5.0 mL) in a sealed tube was added sequentially tributyl(vinyl)stannane (0.027 mL, 0.092 mmol) and lithium chloride (10.7 mg, 0.252 mmol). The reaction mixture was degassed with nitrogen for 5 minutes. Tetrakis(triphenylphosphine)palladium(0) (9.71 mg, 8.40 μmol) was added, and the stirred reaction mixture was heated in an oil bath at 100° C. for 4 h overnight. 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 solid residue was purified by flash silica gel chromatography using a 5% mixture of ethyl acetate in hexane to give the crude product mixture. The crude mixture 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 give 5-methyl-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-4,5-dihydroisoxazolo[4,3-c]quinoline [0.020 g, 0.047 mmol, 56%] as a viscous, tan film. The product had an HPLC ret. time=3.85 min. (condition B); LC/MS M+1=424.1.

Workup

  1. customThe reaction mixture was degassed with nitrogen for 5 minutes
  2. customthe stirred reaction mixture
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionthe residue was diluted with dichloromethane (10 mL)
  5. filtrationfiltered through a pad of Celite
  6. washrinsed with dichloromethane (10 mL)
  7. concentrationThe filtrate was concentrated
  8. customthe solid residue was purified by flash silica gel chromatography
  9. customto give the crude product mixture
  10. customThe crude mixture was chromatographed
  11. 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-8c8ec8fa0a1446e0bd00537e88966812
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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