Water → Tert-butyl 4-(((2-chloro-5-iodopyridin-4-yl)amino)methyl)piperidine-1-carboxylate

HRID 556857ノート

反応式

HRID 556857 の反応式
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([NH2:10])[C:7]([I:11])=[CH:6][N:5]=1.Br[CH2:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.O>CN(C=O)C>[Cl:3][C:4]1[CH:9]=[C:8]([NH:10][CH2:13][CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:16][CH2:15]2)[C:7]([I:11])=[CH:6][N:5]=1

参加物

6

反応物 4

HCID 962WaterHCID 24758Sodium hydride2 回HCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 454803662-Chloro-5-iodopyridin-4-amine

生成物 1

HCID 59613389Tert-butyl 4-(((2-chloro-5-iodopyridin-4-yl)amino)methyl)piperidine-1-carboxylate収率 46%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

NaH (0.098 g, 3.9 mmol) was added to a solution of 2-chloro-5-iodopyridin-4-amine (0.500 g, 1.96 mmol) in DMF (12 mL) and the mixture was stirred for 30 min at r.t. The temperature was then raised to 80° C. and a solution of tert-butyl 4-(bromomethyl)-piperidine-1-carboxylate (1.093 g, 3.93 mmol) in DMF (2 mL) was added. The reaction mixture was stirred at 80° C. for 2 h, then cooled to r.t. NaH (0.050 g, 2.00 mmol) was added and the reaction mixture was heated for 1 h at 80° C. After cooling, water (40 mL) was added and the reaction mixture was partitioned between ethyl acetate and aq. NaHCO3. The organic phase was washed with brine, dried (MgSO4) and concentrated. The crude product was purified by flash silica chromatography, eluting with ethyl acetate and hexane (1/9), to give the title compound as a pink solid (0.405 g, 46%).

後処理

  1. temperatureThe temperature was then raised to 80° C.
  2. stirringThe reaction mixture was stirred at 80° C. for 2 h
  3. temperaturecooled to r.t
  4. temperaturethe reaction mixture was heated for 1 h at 80° C
  5. temperatureAfter cooling
  6. customthe reaction mixture was partitioned between ethyl acetate and aq. NaHCO3
  7. washThe organic phase was washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe crude product was purified by flash silica chromatography
  11. washeluting with ethyl acetate and hexane (1/9)

出典と根拠

ORDレコード
ord-5aab0959a2f846f08f0d22d5f2ad4fc3
出典データセット
uspto-grants-2011_11
特許番号
US08058045B2

反応ノート

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