Sodium Carbonate → 6-Fluoro-3,4-dimethoxy-2-(2-pyridyl)benzonitrile

HRID 1582378노트

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HRID 1582378 반응식
[F:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](I)[C:5]([O:11][CH3:12])=[C:4]([O:13][CH3:14])[CH:3]=1.B([O-])O[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I.C(OCC)(=O)C.O.O1CCOCC1>[F:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[C:5]([O:11][CH3:12])=[C:4]([O:13][CH3:14])[CH:3]=1

참가 물질

10

반응물 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 227212146-Fluoro-2-iodo-3,4-dimethoxybenzonitrileHCID 178514833HCID 178514833, 화합물2회

생성물 1

HCID 98138056-Fluoro-3,4-dimethoxy-2-(2-pyridyl)benzonitrile수율 49.3%

시약·촉매·용매 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

Under nitrogen, stirred dioxane (20 ml) at 80° C. was charged with 6-fluoro-2-iodo-3,4-dimethoxybenzonitrile from Example 1(a) (1.0 g, 3.3 mmol), tetrakis(triphenyl-phosphine) palladium(0) (0.19 g, 0.16 mmol), the pyridyl boronate from Example 1(b) (1.22 g, estimated to be 7.1 mmol), copper(I)iodide (0.25 g, 1.3 mmol), sodium carbonate (0.69 g, 6.5 mmol) and triphenylphosphine (0.17 g, 0.65 mmol) and the resulting brown slurry heated to reflux. Further portions of the pyridyl boronate were added at the following times after the reaction had reached reflux: 0.61 g after 30 mins; 0.61 g after 1 hour; 0.61 g after 1 hour 30 mins; 0.61 g after 2 hours 30 mins; 0.61 g after 3 hours; and 0.30 g after 4 hours. After a total of 5 hours at reflux the reaction was allowed to cool to room temperature, water (10 ml) and ethyl acetate (20 ml) were added and the resulting mixture allowed to stir for 15 mins. After this time, the mixture was filtered through Arbocel™ filter aid and the pad washed with ethyl acetate (20 ml). The phases were separated and the aqueous phase extracted with ethyl acetate (20 ml). The organic phases were combined and evaporated to a brown oil. Acetonitrile was added, the mixture warmed to reflux and left to cool to room temperature overnight. The resulting suspension was filtered to give a cream solid that was dried in vacuo overnight at 45° C. to give 0.42 g of the title product (49%).

후처리

  1. temperaturehad reached reflux
  2. wait0.61 g after 1 hour
  3. wait0.61 g after 1 hour 30 mins
  4. wait0.61 g after 2 hours 30 mins
  5. wait0.61 g after 3 hours
  6. waitand 0.30 g after 4 hours
  7. temperatureAfter a total of 5 hours at reflux the reaction
  8. filtrationAfter this time, the mixture was filtered through Arbocel™
  9. filtrationfilter aid
  10. washthe pad washed with ethyl acetate (20 ml)
  11. customThe phases were separated
  12. extractionthe aqueous phase extracted with ethyl acetate (20 ml)
  13. customevaporated to a brown oil
  14. additionAcetonitrile was added
  15. temperaturethe mixture warmed
  16. temperatureto reflux
  17. waitleft
  18. temperatureto cool to room temperature overnight
  19. filtrationThe resulting suspension was filtered
  20. customto give a cream solid
  21. customthat was dried in vacuo overnight at 45° C.

출처 및 근거

ORD 기록
ord-7495d308c9a040b6888f8539120b865f
출처 데이터셋
uspto-grants-2004_05
특허 번호
US06734303B2

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