Potassium Carbonate → 4-Cyclopropyl-2-fluoro-6-methylbenzamide

HRID 2069706노트

반응식

HRID 2069706 반응식
Br[C:2]1[CH:10]=[C:9]([CH3:11])[C:5]([C:6]([NH2:8])=[O:7])=[C:4]([F:12])[CH:3]=1.[CH:13]1(B(O)O)[CH2:15][CH2:14]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(=O)([O-])[O-].[K+].[K+].[OH-].[NH4+]>C1(C)C=CC=CC=1.O.CCCCCCC.C(OCC)(=O)C>[CH:13]1([C:2]2[CH:10]=[C:9]([CH3:11])[C:5]([C:6]([NH2:8])=[O:7])=[C:4]([F:12])[CH:3]=2)[CH2:15][CH2:14]1

참가 물질

10

반응물 5

HCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 594737734-Bromo-2-fluoro-6-methylbenzamide

생성물 1

HCID 594738034-Cyclopropyl-2-fluoro-6-methylbenzamide

시약·촉매·용매 4

HCID 962Water용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매2회HCID 8900Heptane용매

반응 조건

온도
60 °C

실험 절차

A mixture of 4-bromo-2-fluoro-6-methylbenzamide (10 g), cyclopropylboronic acid (4.87 g, 1.25 eq), tricyclohexylphosphine (725 mg, 0.06 eq), tris (dibenzyllideneacetone)dipalladium(0) chloroform adduct (446 mg, 0.01 eq) and potassium carbonate (17.9 g, 3 eq) in toluene (100 ml) and water (10 ml) was stirred under reflux in an inert (nitrogen) environment for about 24 h. The reaction mixture was then cooled to about 60° C. and treated with 10% aqueous ammonium hydroxide (60 ml) and then with ethyl acetate (60 ml). Layers were separated, the organic phase was washed with brine and filtered to remove particulate material. The extract was concentrated under reduced pressure to about 30 ml to obtain a slurry. This was diluted with heptane (80 ml) and ethyl acetate (20 ml) and then heated to reflux to dissolve all solids. The resulting solution cooled slowly to room temperature to allow the product to crystallize out. The precipitated product was isolated by filtration, washed with ethyl acetate-heptane (1:1) mixture (60 ml), dried under vacuum at about 60° C. to obtain 6.85 g (82.3% isolated yield) of product.

후처리

  1. temperatureunder reflux in an inert (nitrogen) environment for about 24 h
  2. customLayers were separated
  3. washthe organic phase was washed with brine
  4. filtrationfiltered
  5. customto remove particulate material
  6. concentrationThe extract was concentrated under reduced pressure to about 30 ml
  7. customto obtain a slurry
  8. temperatureheated
  9. temperatureto reflux
  10. dissolutionto dissolve all solids
  11. temperatureThe resulting solution cooled slowly to room temperature
  12. customto crystallize out
  13. customThe precipitated product was isolated by filtration
  14. washwashed with ethyl acetate-heptane (1:1) mixture (60 ml)
  15. customdried under vacuum at about 60° C.
  16. customto obtain
  17. custom6.85 g (82.3% isolated yield) of product

출처 및 근거

ORD 기록
ord-9276121b66e54034929eb19fed8b47ed
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299077B2

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