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

HRID 1725768

반응식

HRID 1725768 반응식
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

참가 물질

7

반응물 3

HCID 7912Diisopropylamine2회HCID 31297Methanesulfonyl chloride2회HCID 23084083tert-butyl 4-hydroxy-4-(1H-imidazol-2-yl)piperidine-1-carboxylate

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 14798Sodium Hydroxide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-e19b86e03737427193fd8c369ce3d3b2
출처 데이터셋
uspto-grants-2009_02
특허 번호
US07491737B2

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