Tetrabutylammonium Fluoride → HCID 66799651, compound

HRID 2172730Notes

Reaction equation

HRID 2172730 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)=[CH:10][CH:9]=2)[N:5]=[C:4]([C:21]([O:23][CH3:24])=[O:22])[CH:3]=1.[CH:25](B1OC(C)(C)C(C)(C)O1)=[CH2:26].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:20][C:17]1[CH:18]=[CH:19][C:14]([C:11]2[CH:12]=[CH:13][C:8]([C:6]3[N:5]=[C:4]([C:21]([O:23][CH3:24])=[O:22])[CH:3]=[C:2]([CH:25]=[CH2:26])[CH:7]=3)=[CH:9][CH:10]=2)=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 66801409HCID 66801409, compound2×

Product 1

HCID 66799651HCID 66799651, compoundYield 216.9%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
60 °C

Procedure

To THF (16 mL) degassed by purging argon was added methyl 4-chloro-6-(4′-fluoro-[1,1′-biphenyl]-4-yl)picolinate (compound II, 800 mg, 0.83 mmol), vinyl boronic acid pinacol ester (360 mg, 2.9 mmol), and tetrabutylammonium fluoride (1M in THF, 4.68 mL), and the reaction mixture was degassed. Pd(dppf)Cl2 (85.6 mg, 0.04 mmol) was added and the reaction was degassed for an additional 15 minutes. The reaction mixture was heated at 60° C. in an oil bath for overnight. TLC (silica gel, 4/1 heptane/ethyl acetate) showed the reaction had not gone to completion. Additional reaction time had no effect, so the reaction was cooled, diluted with ethyl acetate, and extracted with brine. The organic layer was dried (sodium sulfate) and concentrated under vacuum to obtain the crude product which was purified by column chromatography (230-400 mesh silica gel, 0-8% ethyl acetate in heptane as eluent) to yield 600 mg of methyl 6-(4′-fluoro-[1,1′-biphenyl]-4-yl)-4-vinylpicolinate.

Workup

  1. customTo THF (16 mL) degassed
  2. customby purging argon
  3. customthe reaction mixture was degassed
  4. customthe reaction was degassed for an additional 15 minutes
  5. temperatureso the reaction was cooled
  6. additiondiluted with ethyl acetate
  7. extractionextracted with brine
  8. dry with materialThe organic layer was dried (sodium sulfate)
  9. concentrationconcentrated under vacuum
  10. customto obtain the crude product which
  11. customwas purified by column chromatography (230-400 mesh silica gel, 0-8% ethyl acetate in heptane as eluent)

Sources & evidence

ORD record
ord-dfab74c1233e4f4a8d3bc941fb26e12f
Source dataset
uspto-grants-2015_06
Patent number
US09056832B2

Reaction notes

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