Diisopropylamine → tert-butyl 4-(1H-imidazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1725768ノート

反応式

HRID 1725768 の反応式
O[C:2]1([C:15]2[NH:16][CH:17]=[CH:18][N:19]=2)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C(NC(C)C)(C)C.CS(Cl)(=O)=O>CN(C=O)C.O.[OH-].[Na+]>[NH:16]1[CH:17]=[CH:18][N:19]=[C:15]1[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH:3]=1

参加物

7

反応物 3

HCID 7912Diisopropylamine2 回HCID 31297Methanesulfonyl chloride2 回HCID 23084083tert-butyl 4-hydroxy-4-(1H-imidazol-2-yl)piperidine-1-carboxylate

生成物 1

HCID 69053296tert-butyl 4-(1H-imidazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate収率 76.6%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 14798Sodium Hydroxide溶媒

実験手順

To a solution of tert-butyl 4-hydroxy-4-(1H-imidazol-2-yl)piperidine-1-carboxylate (10.5 g) and diisopropylamine (13.8 mL, 2.5 equiv.) in anhydrous DMF under N2 at 0° C. was added in one portion of methanesulfonyl chloride (6.19 mL, 2 equiv.). The reaction was stirred at 0° C. for 2 hours when a further 2 equivalents of methanesulfonyl chloride and 2.5 equivalents of diisopropylamine was added and the resulting mixture stirred at room temperature overnight. The mixture was diluted with water (200 mL) and adjusted pH 9 with 1 N NaOH and then extracted with ethyl acetate (3×). The combined ethyl acetate layers was dried over MgSO4, filtered and evaporated. The residue was purified by column chromatography on silica eluting with 5% methanol in dichloromethane with 0.5% ammonium hydroxide to give tert-butyl 4-(1H-imidazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (7.5 g).

後処理

  1. additionwas added
  2. extractionextracted with ethyl acetate (3×)
  3. dry with materialThe combined ethyl acetate layers was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography on silica eluting with 5% methanol in dichloromethane with 0.5% ammonium hydroxide

出典と根拠

ORDレコード
ord-e19b86e03737427193fd8c369ce3d3b2
出典データセット
uspto-grants-2009_02
特許番号
US07491737B2

反応ノート

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