Tributylvinyltin → 3-Phenyl-4-(trifluoromethyl)-5-(7-vinyl-4,5-dihydronaphtho[2,1-d]thiazol-2-yl)isoxazole

HRID 1506420Notes

Reaction equation

HRID 1506420 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:17](=[CH:18][CH:19]=1)[C:16]1[S:15][C:14]([C:20]3[O:24][N:23]=[C:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:21]=3[C:31]([F:34])([F:33])[F:32])=[N:13][C:12]=1[CH2:11][CH2:10]2)(=O)=O.[CH2:37]([Sn](CCCC)(CCCC)C=C)[CH2:38]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:25]1([C:22]2[C:21]([C:31]([F:33])([F:34])[F:32])=[C:20]([C:14]3[S:15][C:16]4[C:17]5[C:9](=[CH:8][C:7]([CH:37]=[CH2:38])=[CH:19][CH:18]=5)[CH2:10][CH2:11][C:12]=4[N:13]=3)[O:24][N:23]=2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 81998TributylvinyltinHCID 433294Lithium ChlorideHCID 866699002-(3-Phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl trifluoromethanesulfonate

Product 1

HCID 671705843-Phenyl-4-(trifluoromethyl)-5-(7-vinyl-4,5-dihydronaphtho[2,1-d]thiazol-2-yl)isoxazole

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl trifluoromethanesulfonate (Preparation 56D, 0.451 g, 0.825 mmol), tributyl(vinyl)tin (0.265 mL, 0.908 mmol), and lithium chloride (0.105 g, 2.476 mmol) in dioxane (5.0 mL) was placed in a microwave reaction vessel. To this was added tetrakis(triphenylphosphine)palladium(0) (0.095 g, 0.083 mmol) and argon was bubbled into the mixture for 3 min. The vessel was capped and the reddish brown mixture was immersed in a 100° C. oil bath. After 6 h of stirring, the reaction mixture was cooled to room temperature. EtOAc was added and the contents were stirred for 30 min. It was then filtered through a plug of Celite. The filter cake was washed with EtOAc (2×). The combined organic layers were then concentrated in vacuo. The residue was suspended in ether and stirred vigorously for another 30 min., filtered through a plug of celite and the filter cake washed with ether (2×). The combined organic layers were concentrated and chromatographed. The product had an LC ret. time=3.996 min. (condition: Start % B=50, Final % B=100, Gradient Time=4 min, Flow Rate=4 ml/min, Wavelength=220, Solvent Pair=MeOH−H2O−TFA; Solvent A=10% MeOH—90% H2O−0.1% TFA; Solvent B=90% MeOH−10% H2O−0.1% TFA; Column 1=1: Waters Sunfire C18 4.6×50 mm (4 min. grad)); LC/MS M+1=425.07.

Workup

  1. customwas placed in a microwave reaction vessel
  2. customwas bubbled into the mixture for 3 min
  3. customThe vessel was capped
  4. customwas immersed in a 100° C.
  5. additionEtOAc was added
  6. stirringthe contents were stirred for 30 min
  7. filtrationIt was then filtered through a plug of Celite
  8. washThe filter cake was washed with EtOAc (2×)
  9. concentrationThe combined organic layers were then concentrated in vacuo
  10. stirringstirred vigorously for another 30 min.
  11. filtrationfiltered through a plug of celite
  12. washthe filter cake washed with ether (2×)
  13. concentrationThe combined organic layers were concentrated
  14. customchromatographed
  15. customB=100, Gradient Time=4 min, Flow Rate=4 ml/min, Wavelength=220, Solvent Pair=MeOH−H2O−TFA
  16. customC18 4.6×50 mm (4 min. grad)

Sources & evidence

ORD record
ord-03c6469c7e5047dd8f1dc7cdd249dcd8
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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