1,4-Dioxane → HCID 86695924, 화합물

HRID 870931노트

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HRID 870931 반응식
Cl[C:2]1[C:7]([C:8]([O-:10])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=1[F:11].[Cl:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[C:15]([F:22])[CH:14]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOC[CH2:32]1>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[C:7]([C:8]([O:10][CH3:32])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=2[F:11])=[C:15]([F:22])[CH:14]=1

참가 물질

7

반응물 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 86335698HCID 86335698, 화합물

생성물 1

HCID 86695924HCID 86695924, 화합물수율 50%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매

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온도
80 °C

실험 절차

To a solution of 4-chloro-5-fluoronicotinate (1.2 g, 6.33 mmol) in 1,4-dioxane (12 mL) and water (0.5 mL) was added (4-chloro-2-fluorophenyl)boronic acid (1.214 g, 6.96 mmol) and potassium phosphate, dibasic (2.205 g, 12.66 mmol). To this mixture, PdCl2(dppf) (0.371 g, 0.506 mmol) was added and the solution purged with N2 for 10 min then heated to 80° C. for 12 h. The mixture was cooled to room temperature and water (25 mL) was added. The solution was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine (25 mL) and concentrated under reduced pressure to afford the residue which was purified by silica gel column using a gradient of ethyl acetate in hexanes to afford methyl 4-(4-chloro-2-fluorophenyl)-5-fluoronicotinate (900 mg, 3.17 mmol, 50% yield) as a yellow solid. LCMS (ESI) m/e 284.0 [(M+H)+, calcd for C13H9ClF2NO2 284.0]; LC/MS retention time (Method F): tR=1.01 min.

후처리

  1. customthe solution purged with N2 for 10 min
  2. temperatureThe mixture was cooled to room temperature
  3. additionwater (25 mL) was added
  4. extractionThe solution was extracted with ethyl acetate (3×25 mL)
  5. washThe combined organic layers were washed with brine (25 mL)
  6. concentrationconcentrated under reduced pressure
  7. customto afford the residue which
  8. customwas purified by silica gel column

출처 및 근거

ORD 기록
ord-8e74e5d14c3a456d99b6dd438aafd92c
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969564B2

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