Tris(1,1-dimethylethyl)phosphine → Methyl 6-(2,6-difluoro-4-methoxyphenyl)-5-fluoropicolinate

HRID 705183노트

반응식

HRID 705183 반응식
Br[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[F:12].[F:13][C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[C:16]([F:22])[C:15]=1B(O)O.[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1COCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:13][C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[C:16]([F:22])[C:15]=1[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[F:12]

참가 물질

8

반응물 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 162174242,6-Difluoro-4-methoxybenzeneboronic acidHCID 46311204Methyl 6-bromo-5-fluoropyridine-2-carboxylate

생성물 1

HCID 59226460Methyl 6-(2,6-difluoro-4-methoxyphenyl)-5-fluoropicolinate수율 85%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
80 °C

실험 절차

To a solution of methyl 6-bromo-5-fluoropicolinate (1.0 equiv.) in THF and water (10:1, 0.1 M) was added 2,6-difluoro-4-methoxyphenylboronic acid (2.5 equiv.) and potassium fluoride (3.3 equiv.). The reaction was degassed with nitrogen, then Pd2(dba)3 (0.25 equiv.) and tri-tert-butylphosphine (0.5 equiv.) were added and the reaction was heated to 80° C. for one hour. LC/MS analysis indicated complete conversion of the starting material to product. The reaction was cooled to room temperature, then concentrated in vacuo and fused to silica gel. The crude product was purified by ISCO flash chromatography eluting with ethyl acetate and hexanes (0% to 30% ethyl acetate) to provide methyl 6-(2,6-difluoro-4-methoxyphenyl)-5-fluoropicolinate as a white solid in 85% yield. LC/MS=298.0 (M+H), Rt=0.89 min.

후처리

  1. customThe reaction was degassed with nitrogen
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by ISCO flash chromatography
  5. washeluting with ethyl acetate and hexanes (0% to 30% ethyl acetate)

출처 및 근거

ORD 기록
ord-f12289236517459faab528343748fba3
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09173883B2

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