Hydrochloric Acid → 4-(5-Aminopyridin-2-yl)-1-(2-hydroxy-2-methylpropyl)piperidine-4-carbonitrile

HRID 1748519ノート

反応式

HRID 1748519 の反応式
C(=[NH:14])(C1C=CC=CC=1)C1C=CC=CC=1.Br[C:16]1[CH:17]=[CH:18][C:19]([C:22]2([C:33]#[N:34])[CH2:27][CH2:26][N:25]([CH2:28][C:29]([OH:32])([CH3:31])[CH3:30])[CH2:24][CH2:23]2)=[N:20][CH:21]=1.C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].Cl.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[NH2:14][C:16]1[CH:17]=[CH:18][C:19]([C:22]2([C:33]#[N:34])[CH2:27][CH2:26][N:25]([CH2:28][C:29]([OH:32])([CH3:31])[CH3:30])[CH2:24][CH2:23]2)=[N:20][CH:21]=1

参加物

10

反応物 6

HCID 313Hydrochloric AcidHCID 136809Benzophenone imineHCID 516892Sodium BicarbonateHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 23676156Sodium t-butoxideHCID 866924674-(5-Bromopyridin-2-yl)-1-(2-hydroxy-2-methylpropyl)piperidine-4-carbonitrile

生成物 1

HCID 866924684-(5-Aminopyridin-2-yl)-1-(2-hydroxy-2-methylpropyl)piperidine-4-carbonitrile収率 81.1%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
120 °C

実験手順

Benzophenonimine (2.22 g) was added to a suspension of 4-(5-bromopyridin-2-yl)-1-(2-hydroxy-2-methylpropyl)piperidine-4-carbonitrile (3.95 g), palladium (II) acetate (328 mg), racemic-2-(di-tert-butylphosphino)-1,1′-binaphthyl (909 mg) and sodium tert-butoxide (1.68 g) in toluene (29 ml), and stirred at 120° C. for 2.5 hours. The reaction solution was left stand, a mixture of concentrated hydrochloric acid (2 ml) and water (6 ml) were added at 60-80° C. and stirred at room temperature. A saturated aqueous solution of sodium bicarbonate was added to the reaction solution and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified with basic silica gel column chromatography (n-hexane/ethyl acetate) to give the titled compound (2.6 g) as a pale yellow solid.

後処理

  1. waitThe reaction solution was left stand
  2. additionwere added at 60-80° C.
  3. stirringstirred at room temperature
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified with basic silica gel column chromatography (n-hexane/ethyl acetate)

出典と根拠

ORDレコード
ord-407f97cfb8a643a19128679650219744
出典データセット
uspto-grants-2015_10
特許番号
US09150555B2

反応ノート

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