1-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine → 4-[2-(5-Benzylcarbamoyl-6-chloro-2-methylsulfanylpyrimidin-4-yloxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester

HRID 645521ノート

反応式

HRID 645521 の反応式
[CH2:1]([NH:8][C:9]([C:11]1[C:12]([Cl:20])=[N:13][C:14]([S:18][CH3:19])=[N:15][C:16]=1Cl)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][CH:37]([CH2:40][CH2:41][OH:42])[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28]>C1COCC1>[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][CH:37]([CH2:40][CH2:41][O:42][C:16]2[C:11]([C:9](=[O:10])[NH:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[C:12]([Cl:20])[N:13]=[C:14]([S:18][CH3:19])[N:15]=2)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28]

参加物

5

反応物 3

HCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidineHCID 23665647Potassium tert-butoxideHCID 86627801N-benzyl-4,6-dichloro-2-(methylthio)pyrimidine-5-carboxamide

生成物 1

HCID 866278024-[2-(5-Benzylcarbamoyl-6-chloro-2-methylsulfanylpyrimidin-4-yloxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of 4,6-dichloro-2-methylsulfanylpyrimidine-5-carboxylic acid benzylamide (3 mmol) in THF (20 mL) is added KOtBu (3.6 mmol) at 0° C. under N2. After stirred at 0° C. for 20 min, the above mixture is added dropwise to a solution of 4-(2-hydroxyethyl)piperidine-1-carboxylic acid tert-butyl ester (3.3 mmol) in THF (20 mL) at −78° C. The resulting mixture is gradually warm up to −30° C. over 2.5 h. The reaction is quenched by the addition of H2O. The mixture is extracted twice with AcOEt. The organic layer is dried over Na2SO4, filtered, and concentrated to give 4-[2-(5-benzylcarbamoyl-6-chloro-2-methylsulfanylpyrimidin-4-yloxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester as a white solid; 1H-NMR (CDCl3), δ 1.07-1.17 (2H, m), 1.48 (9H, s), 1.62-1.70 (2H, m), 2.54 (3H, s), 2.64 (2H, br t), 4.06 (2H, m), 4.45 (2H, t), 4.64 (2H, d), 6.06 (1H, t), 7.30-7.34 (2H, m), 7.35-7.36 (3H, m).

後処理

  1. temperatureThe resulting mixture is gradually warm up to −30° C. over 2.5 h
  2. customThe reaction is quenched by the addition of H2O
  3. extractionThe mixture is extracted twice with AcOEt
  4. dry with materialThe organic layer is dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-bcee3dc6e04a4117a90ecb420e86a0ef
出典データセット
uspto-grants-2010_04
特許番号
US07704996B2

反応ノート

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