Citric Acid → 4-Amino-5-Cyano-2-fluoro-6-methylbiphenyl-3-yl cyclobutanecarboxylate

HRID 17498

반응식

HRID 17498 반응식
[NH2:1][C:2]1[C:9]([OH:10])=[C:8]([F:11])[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:6]([CH3:18])[C:3]=1[C:4]#[N:5].C(N(CC)CC)C.[CH:26]1([C:30](Cl)=[O:31])[CH2:29][CH2:28][CH2:27]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(#N)C>[CH:26]1([C:30]([O:10][C:9]2[C:8]([F:11])=[C:7]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:6]([CH3:18])=[C:3]([C:4]#[N:5])[C:2]=2[NH2:1])=[O:31])[CH2:29][CH2:28][CH2:27]1

참가 물질

6

반응물 4

HCID 311Citric AcidHCID 8471TriethylamineHCID 78705Cyclobutanecarbonyl chlorideHCID 860974464-Amino-3-cyano-6-fluoro-5-hydroxy-2-methylbiphenyl

생성물 1

HCID 866308594-Amino-5-Cyano-2-fluoro-6-methylbiphenyl-3-yl cyclobutanecarboxylate수율 85%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
0 °C

실험 절차

Under nitrogen atmosphere, 2-amino-5-phenyl-4-fluoro-3-hydroxy-6-methylbenzonitrile (I-41) (250 mg, 1.03 mmol) was dissolved in acetonitrile (0.10 ml), and cooled to 0° C. Triethylamine (244 μl, 1.75 mmol) and cyclobutanecarbonyl chloride (177 μl, 1.55 mmol) were dropwise added to the solution, followed by stirring at room temperature for 1 hour. 10% citric acid was added to the reaction liquid, and the solvent was evaporated away under, reduced pressure. Ethyl acetate was added to the resulting residue, followed by washing with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure. The resulting residue was subjected to silica gel column chromatography, and the eluate with ethyl acetate/hexane (1:4, v/v) gave the entitled compound (283 mg, 85%) as a white solid.

후처리

  1. customthe solvent was evaporated away under, reduced pressure
  2. additionEthyl acetate was added to the resulting residue
  3. washby washing with saturated brine
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated away under reduced pressure

출처 및 근거

ORD 기록
ord-6306fbf97e3d4cb984eb4bec6402c498
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737166B2

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