Triphenylphosphine → 4-[6-(5-Fluoro-2-methoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester

HRID 1020045

반응식

HRID 1020045 반응식
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:26])[NH:18][C:19]2[CH:24]=[C:23](Cl)[N:22]=[CH:21][N:20]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:27][C:28]1[CH:29]=[CH:30][C:31]([O:37][CH3:38])=[C:32](B(O)O)[CH:33]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:26])[NH:18][C:19]2[CH:24]=[C:23]([C:30]3[CH:29]=[C:28]([F:27])[CH:33]=[CH:32][C:31]=3[O:37][CH3:38])[N:22]=[CH:21][N:20]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

7

반응물 3

HCID 11776TriphenylphosphineHCID 27826735-Fluoro-2-methoxyphenylboronic acidHCID 595089554-(6-Chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester

생성물 1

HCID 595090204-[6-(5-Fluoro-2-methoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester수율 52.5%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 10340Sodium Carbonate용매HCID 312751,4-Dioxane용매

반응 조건

온도
110 °C

실험 절차

To a stirred mixture of 4-(6-chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester (VIII) (0.60 g, 1.6 mmol) and 5-fluoro-2-methoxy-phenylboronic acid (0.300 g, 1.76 mmol) in saturated sodium carbonate solution (5 ml) and 1,4-dioxane (5 ml) was added palladium(II) acetate (0.072 g, 0.32 mmol) followed by triphenylphosphine (0.084 g, 0.32 mmol) at room temperature under an atmosphere of nitrogen. The resulting mixture was heated to reflux at 110° C. for one hour and the reaction monitored by TLC. The reaction mixture was filtered through a celite bed and the filtrate was extracted with ethyl acetate (3×100 ml). The organic layers were separated, combined, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel, elution with 50% ethyl acetate/n-hexanes) to afford 4-[6-(5-fluoro-2-methoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester (XXI) (0.39 g, 52%) as a pale yellow oil.

후처리

  1. temperatureThe resulting mixture was heated
  2. filtrationThe reaction mixture was filtered through a celite bed
  3. extractionthe filtrate was extracted with ethyl acetate (3×100 ml)
  4. customThe organic layers were separated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by flash column chromatography (silica gel, elution with 50% ethyl acetate/n-hexanes)

출처 및 근거

ORD 기록
ord-f9d296e174124e29815262483b6e42e0
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716296B2

연결된 노트

불러오는 중…