Water → 3-Bromo-5-fluoro-2-methyl pyridine

HRID 1631306노트

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HRID 1631306 반응식
Br[C:2]1[C:7]([Br:8])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1.[CH3:10]B(O)O.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:8][C:7]1[C:2]([CH3:10])=[N:3][CH:4]=[C:5]([F:9])[CH:6]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 139377Methylboronic AcidHCID 228320932,3-Dibromo-5-fluoropyridine

생성물 1

HCID 668478723-Bromo-5-fluoro-2-methyl pyridine수율 32.2%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

2,3-Dibromo-5-fluoropyridine (5.0 g, 19.6 mmol), Pd(PPh3)4 (1.13 g, 0.98 mmol) and methyl boronic acid (3.52 g, 58.9 mmol) were combined in dioxane (50 mL) then treated with K2CO3 (8.13, 58.9 mmol) and water (10 mL). The mixture was purged with N2 then heated to 110° C. in a sealed vessel for 16 hours. The cooled mixture was partitioned between water (100 mL) and EtOAc (50 mL) and the layers separated. The aqueous layer was extracted with EtOAc (2×50 mL) and the combined organic phases were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography eluting with 1-3% EtOAc/hexanes to afford the product as a white solid (1.20 g, 32% yield). MS (apci) m/z=190.2 (M+).

후처리

  1. customThe mixture was purged with N2
  2. customThe cooled mixture was partitioned between water (100 mL) and EtOAc (50 mL)
  3. customthe layers separated
  4. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  5. washthe combined organic phases were washed with brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography
  10. washeluting with 1-3% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-bf065f4376e44ae3b8dc28b978f251c0
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791123B2

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