4-Bromopyridinium chloride → HCID 59486385, compound

HRID 1694289Notes

Reaction equation

HRID 1694289 reaction equation
Cl.Br[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.C(O[C:14]([N:16]1[CH2:21][CH2:20][C:19]2(CCNCC2)C[CH2:17]1)=O)(C)(C)C.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.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]>[CH:21]1([N:16]2[CH2:14][CH2:3][C:8]3([CH2:4][CH2:5][NH:6][CH2:7]3)[CH2:17]2)[CH2:19][CH2:20]1

Participants

7

Reactant 3

HCID 881004-Bromopyridinium chlorideHCID 634876Binap, (A+-)-HCID 15296367tert-Butyl 3,9-diazaspiro[5.5]undecane-3-carboxylate

Product 1

HCID 59486385HCID 59486385, compoundYield 45%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Sodium tert-butylate (4 mmol) was added to a solution of 4-bromopyridine hydrochloride (1.9 mmol) in dry toluene (10 ml) under argon, followed by 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (1.6 mmol) in toluene (5 ml). Argon was added to the mixture for 15 min, then (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.123 mmol) and tris(dibenzylidene acetone)dipalladium (0.041 mmol) were added. The mixture was heated at 90° C. for 4 h and the reaction progress was monitored by thin-layer chromatography. On completion of the reaction the mixture was diluted with ethyl acetate (100 ml) and extracted with water and saturated sodium chloride solution, dried (Na2SO4), filtered and concentrated to small volume. The crude product was purified by column chromatography (3% methanol in DCM). Yield: 45% 2. TFA (13 eq.) was added to a DCM solution (10 ml/mmol) of tert-butyl 9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylate (1 eq.) at 0° C. and the mixture was stirred for 2 h at RT. The solvent was removed and the product was dried under vacuum. The crude product was used in the following stage with no further purification. Yield: quantitative

Workup

  1. additionArgon was added to the mixture for 15 min
  2. customOn completion of the reaction the mixture
  3. extractionextracted with water and saturated sodium chloride solution
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated to small volume
  7. customThe crude product was purified by column chromatography (3% methanol in DCM)

Sources & evidence

ORD record
ord-64d8577c69b7424bad4c4365e0786957
Source dataset
uspto-grants-2012_04
Patent number
US08158628B2

Reaction notes

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