2,5-Dihydrofuran → 6-(Cyclopropylmethoxy)-5-(4,5-dihydrofuran-2-yl)-pyridine-2-carboxylic acid methyl ester

HRID 927530

반응식

HRID 927530 반응식
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](Br)=[C:7]([O:12][CH2:13][CH:14]2[CH2:16][CH2:15]2)[N:6]=1)=[O:4].[O:17]1[CH2:21][CH:20]=[CH:19][CH2:18]1.C([O-])(=O)C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[CH3:40][O:41][C:42]([C:44]1[CH:49]=[CH:48][C:47]([C:50]2[CH2:51][O:52][CH2:53][CH:54]=2)=[C:46]([O:55][CH2:56][CH:57]2[CH2:59][CH2:58]2)[N:45]=1)=[O:43]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:40][O:41][C:42]([C:44]1[CH:49]=[CH:48][C:47]([C:50]2[CH2:51][O:52][CH2:53][CH:54]=2)=[C:46]([O:55][CH2:56][CH:57]2[CH2:59][CH2:58]2)[N:45]=1)=[O:43].[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:18]2[O:17][CH2:21][CH2:20][CH:19]=2)=[C:7]([O:12][CH2:13][CH:14]2[CH2:16][CH2:15]2)[N:6]=1)=[O:4]

참가 물질

10

반응물 5

HCID 155702,5-DihydrofuranHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 517045Sodium AcetateHCID 71087286Methyl 5-bromo-6-(cyclopropylmethoxy)picolinateHCID 710874196-(Cyclopropylmethoxy)-5-(2,5-dihydrofuran-3-yl)-pyridine-2-carboxylic acid methyl ester

생성물 2

HCID 710874196-(Cyclopropylmethoxy)-5-(2,5-dihydrofuran-3-yl)-pyridine-2-carboxylic acid methyl esterHCID 710879866-(Cyclopropylmethoxy)-5-(4,5-dihydrofuran-2-yl)-pyridine-2-carboxylic acid methyl ester수율 79%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
120 °C

실험 절차

A mixture of 5-bromo-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid methyl ester (0.5 g, 1.7 mmol), 2,5-dihydrofuran (CAN 1708-29-8, 1.2 g, 17 mmol), palladium(II) acetate (CAN 3375-31-3, 0.02 g, 0.09 mmol), sodium acetate (0.17 g, 2 mmol) and tri-tert-butylphosphine (CAN 13716-12-6, 0.037 g, 0.2 mmol) in DMF (10 mL) was stirred at 120° C. for 2.5 h under a nitrogen atmosphere. Water was poured into the reaction mixture and the resulting mixture was extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and evaporated. The residue was purified by column chromatography (silica gel, 10 g, eluting with 5% ethyl acetate in petroleum ether) to yield 6-(cyclopropylmethoxy)-5-(2,5-dihydrofuran-3-yl)-pyridine-2-carboxylic acid methyl ester (b1) and 6-(cyclopropylmethoxy)-5-(4,5-dihydrofuran-2-yl)-pyridine-2-carboxylic acid methyl ester (b2) (mixture b1:b2=3:2, 0.38 g, 1.4 mmol, 79%) as yellow oil; MS (EI): m/e=376.1 [M+H]+.

후처리

  1. extractionthe resulting mixture was extracted with ethyl acetate (3×30 mL)
  2. washThe combined organic extracts were washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customevaporated
  5. customThe residue was purified by column chromatography (silica gel, 10 g, eluting with 5% ethyl acetate in petroleum ether)

출처 및 근거

ORD 기록
ord-8bc41ed249044ad4a98a9d0634331c0c
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290451B2

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