2,6-Di-tert-butyl-4-methylphenol → 4-(4-Vinyl-5-isoquinolyl)amino-1-(tert-butoxycarbonyl)piperidine

HRID 1373064Notes

Reaction equation

HRID 1373064 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:5]=[N:4][CH:3]=1.[CH2:26](C([Sn])=C(CCCC)CCCC)[CH2:27]CC.C(C1C(O)=C(C(C)(C)C)C=C(C)C=1)(C)(C)C.[F-].[K+]>C1(C)C=CC=CC=1.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>[CH:26]([C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:5]=[N:4][CH:3]=1)=[CH2:27]

Participants

7

Reactant 4

HCID 314042,6-Di-tert-butyl-4-methylphenolHCID 522689Potassium FluorideHCID 219799724-(4-Bromo-5-isoquinolyl)amino-1-(tert-butoxycarbonyl)piperidineHCID 53438229Tri(butyl)vinyltin

Product 1

HCID 219799424-(4-Vinyl-5-isoquinolyl)amino-1-(tert-butoxycarbonyl)piperidine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of Intermediate 6 (8.00 g), tri(n-butyl)vinyltin (8.63 ml), tetrakis(triphenylphosphine)palladium(0) (455 mg), and 2,6-di-tert-butyl-p-cresol (8.7 mg) in toluene (120 ml) was stirred at 110° C. for 2 hours. The reaction mixture was cooled to room temperature, then added with 10% aqueous potassium fluoride (120 ml), and stirred for 15 hours. After the precipitates were removed by filtration, the organic layer was separated, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1) to obtain the title compound (6.72 g).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringstirred for 15 hours
  3. customAfter the precipitates were removed by filtration
  4. customthe organic layer was separated
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-fdeb0d8ab2bd48f9bf688e687a0f3bb3
Source dataset
uspto-grants-2007_01
Patent number
US07160894B2

Reaction notes

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