4-Bromopyridinium chloride → HCID 59486385, 화합물

HRID 1694289노트

반응식

HRID 1694289 반응식
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

참가 물질

7

반응물 3

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

생성물 1

HCID 59486385HCID 59486385, 화합물수율 45%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

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

후처리

  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)

출처 및 근거

ORD 기록
ord-64d8577c69b7424bad4c4365e0786957
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08158628B2

반응 노트

불러오는 중…