Sodium Bicarbonate → 3-Amino-6-(tetrahydropyran-4-yl)pyridine

HRID 1748499Notes

Reaction equation

HRID 1748499 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.Br[C:30]1[CH:31]=[CH:32][C:33]([CH:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[N:34][CH:35]=1.[F-].C([N+:47](CCCC)(CCCC)CCCC)CCC.C(=O)(O)[O-].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCCC1.C1(C)C=CC=CC=1>[O:39]1[CH2:40][CH2:41][CH:36]([C:33]2[N:34]=[CH:35][C:30]([NH2:47])=[CH:31][CH:32]=2)[CH2:37][CH2:38]1

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 2733832Lithium HexamethyldisilazideHCID 22502735HCID 22502735, compoundHCID 44558591Tri-t-butylphosphine fluoroborate

Product 1

HCID 866924513-Amino-6-(tetrahydropyran-4-yl)pyridine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

After 1.0M toluene-solution (9.8 ml) of lithium bis(trimethylsilyl)amide was added to bis(dibenzylideneacetone)palladium (0) (67 mg) and tri-tert-butylphosphine tetrafluoroborate (118 mg) at 70° C. under an atmosphere of nitrogen, a toluene solution (8.2 ml) of 5-bromo-2-(tetrahydro-2H-pyran-4-yl)pyridine (1.97 g) was added dropwise and stirred at the same temperature for 0.5 hour. Next, the reaction solution was cooled to room temperature, 1.0M tetrahydrofuran-solution (7.0 ml) of tetrabutylammonium fluoride was added and stirred at the same temperature for 1.5 hours. After completion of the reaction, a saturated aqueous solution of sodium bicarbonate was added and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate) to give the titled compound (1.1 g) as a white solid.

Workup

  1. stirringstirred at the same temperature for 1.5 hours
  2. customAfter completion of the reaction
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-9f7957d5786a4d1384289942c085bd20
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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