Potassium Fluoride → Methyl 4-amino-3-chloro-6-(3-fluoro-4-(trifluoromethyl)phenyl)picolinate

HRID 516550ノート

反応式

HRID 516550 の反応式
[NH2:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[Cl:13].[F:14][C:15]1[CH:16]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:18]=[CH:19][C:20]=1[C:21]([F:24])([F:23])[F:22].[F-].[K+]>C(#N)C.O.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[CH:7]=[C:6]([C:17]2[CH:18]=[CH:19][C:20]([C:21]([F:23])([F:24])[F:22])=[C:15]([F:14])[CH:16]=2)[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[Cl:13]

参加物

7

反応物 3

HCID 522689Potassium FluorideHCID 22677331Methyl 4-amino-3,6-dichloropyridine-2-carboxylateHCID 467390543-Fluoro-4-(trifluoromethyl)phenylboronic acid pinacol ester

生成物 1

HCID 90409861Methyl 4-amino-3-chloro-6-(3-fluoro-4-(trifluoromethyl)phenyl)picolinate収率 57.4%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 8857Ethyl Acetate溶媒HCID 18373917Acetonitrile--water (1/1)溶媒

実験手順

Methyl 4-amino-3,6-dichloropicolinate (630 mg, 2.85 mmol), 2-(3-fluoro-4-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.06 g, 3.65 mmol, 1.3 equiv), bis(triphenylphosphine)palladium(II) chloride (209 mg, 0.30 mmol, 0.1 equiv), and potassium fluoride (510 mg, 8.8 mmol, 3 equiv) in acetonitrile/water (8 mL, 3:1) was capped in a 25-mL vial on a Biotage Initiator™ microwave reactor for 20 min at 115° C., with external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude compound was loaded onto a Celite™ cartridge and dried in vacuum oven. Purification by reverse-phase flash chromatography (0-60, 60, 60-100% acetonitrile/water) afforded the title compound as a white solid (0.57 g, 57%).

後処理

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customdried in vacuum oven
  7. customPurification by reverse-phase flash chromatography (0-60, 60, 60-100% acetonitrile/water)

出典と根拠

ORDレコード
ord-0f849c1f5d18405e85e02b41ae6fcc65
出典データセット
uspto-grants-2015_08
特許番号
US09113629B2

反応ノート

読み込み中…