4-Bromopyridinium chloride → HCID 59486385、化合物

HRID 1694289ノート

反応式

HRID 1694289 の反応式
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

参加物

7

反応物 3

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

生成物 1

HCID 59486385HCID 59486385、化合物収率 45%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

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

後処理

  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)

出典と根拠

ORDレコード
ord-64d8577c69b7424bad4c4365e0786957
出典データセット
uspto-grants-2012_04
特許番号
US08158628B2

反応ノート

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