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

HRID 879095ノート

反応式

HRID 879095 の反応式
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]

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-3efd511d7f024290b878110ceaf2bfd8
出典データセット
uspto-grants-2015_03
特許番号
US08987457B2

反応ノート

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