4-Bromopyridinium chloride → HCID 59486385, Verbindung

Temperatur

90 °C

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

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)

ORD-Eintrag

ord-64d8577c69b7424bad4c4365e0786957

Quelldatensatz

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08158628B2