2,6-Di-tert-butyl-4-methylphenol → Ethyl 1-cyclopropyl-6,8-difluoro-7-vinyl-4-oxo-1,4-dihydro-quinoline-3-carboxylate

HRID 2166494Notes

Reaction equation

HRID 2166494 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[C:10]([F:26])[C:11](OS(C(F)(F)F)(=O)=O)=[C:12]([F:17])[CH:13]=2)[N:8]([CH:27]2[CH2:29][CH2:28]2)[CH:7]=1)=[O:5])[CH3:2].[CH:30]([Sn](CCCC)(CCCC)CCCC)=[CH2:31].[Li+].[Cl-].C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C.[F-].[NH+]1C=CC=CC=1>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.N1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[C:10]([F:26])[C:11]([CH:30]=[CH2:31])=[C:12]([F:17])[CH:13]=2)[N:8]([CH:27]2[CH2:28][CH2:29]2)[CH:7]=1)=[O:5])[CH3:2]

Participants

10

Reactant 5

HCID 314042,6-Di-tert-butyl-4-methylphenolHCID 81998TributylvinyltinHCID 433294Lithium ChlorideHCID 13989026HF-PyridineHCID 156368801-Cyclopropyl-7-trifluoromethylsulfonyloxy-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid ethyl ester

Product 1

HCID 15636884Ethyl 1-cyclopropyl-6,8-difluoro-7-vinyl-4-oxo-1,4-dihydro-quinoline-3-carboxylateYield 74.1%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Into a properly equipped flask was added 2.0 g (4.52 mmoles) Compound 3 and 24 ml dry THF. While flushing with nitrogen, 1.36 ml (4.68 mmoles) of vinyltributyltin was added along with 0.58 g (13.56 mmoles) LiCl and, 0.070 g (0.10 mmoles) Pd(PPh3)2Cl2. A couple crystals of 2,6-di-tert-butyl4-methyl phenol was also added just before heating. The reaction was heated to 60°-65° C. for 21 hours after which it turned black and a black precipitate was present. The reaction was cooled to room temperature and 1 ml of pyridine and 2 ml of pyridinium fluoride were added and the reaction allowed to stir overnight. THF was added and the reaction filtered through a celite pad and poured into water. The precipitate formed was collected to give 2.0 g of crude product which was taken up in CH2Cl2 and run through a short silica gel column eluting with dichloromethane to start and slowly increasing polarity to 1% methanol in dichloromethane. The fractions containing product were evaporated in vacuo to give 1.07 g of (4), 74% yield.

Workup

  1. temperaturebefore heating
  2. temperatureThe reaction was heated to 60°-65° C. for 21 hours after which it
  3. filtrationthe reaction filtered through a celite pad
  4. additionpoured into water
  5. customThe precipitate formed
  6. customwas collected
  7. customto give 2.0 g of crude product which
  8. washeluting with dichloromethane
  9. temperatureslowly increasing polarity to 1% methanol in dichloromethane
  10. additionThe fractions containing product
  11. customwere evaporated in vacuo

Sources & evidence

ORD record
ord-f65a80c69ee444e7ac0975aab8b09a13
Source dataset
uspto-grants-1990_07
Patent number
US04945160

Reaction notes

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