Acetonitrile → Methyl 4-amino-5-fluoro-6-(3-fluoro-4-(trifluoromethyl)phenyl)picolinate

HRID 407227ノート

反応式

HRID 407227 の反応式
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=1.[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+].CC#N>CCOC(C)=O.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.O>[NH2:1][C:2]1[C:7]([F:8])=[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:10]([O:12][CH3:13])=[O:11])[CH:3]=1

参加物

8

反応物 4

HCID 6342AcetonitrileHCID 522689Potassium FluorideHCID 467390543-Fluoro-4-(trifluoromethyl)phenylboronic acid pinacol esterHCID 86668302Methyl 4-amino-6-chloro-5-fluoropicolinate

生成物 1

HCID 71150567Methyl 4-amino-5-fluoro-6-(3-fluoro-4-(trifluoromethyl)phenyl)picolinate収率 70.3%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
115 °C

実験手順

To a 5 mL microwave vial was added methyl 4-amino-6-chloro-5-fluoropicolinate (500 mg, 2.44 mmol), 2-(3-fluoro-4-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (851 mg, 2.93 mmol), potassium fluoride (KF; 369 mg, 6.35 mmol), and PdCl2(PPh3)2 (172 mg, 0.24 mmol). Subsequently, CH3CN (3.0 mL) and H2O (3.0 mL) were added, and the reaction vial was sealed and heated in a Biotage microwave at 115° C. for 20 min. The reaction mixture was cooled to room temperature and diluted with EtOAc (5 mL). The layers were separated and the aqueous phase was extracted with EtOAc (2×2 mL). The organic extracts were combined, dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified using a Teledyne ISCO purification system with a gradient eluent system of EtOAc and hexanes to yield the title compound as a yellow solid (570 mg, 70%): 1H NMR (400 MHz, DMSO-d6) δ 7.94 (dt, J=12.3, 6.2 Hz, 3H), 7.52 (d, J=6.4 Hz, 1H), 6.80 (s, 2H), 3.86 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ −59.96, −59.99, −115.69, −144.18, −144.20; ESIMS m/z 333.21 ([M+H]+).

後処理

  1. customthe reaction
  2. customvial was sealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with EtOAc (2×2 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified
  10. customa Teledyne ISCO purification system with a gradient eluent system of EtOAc and hexanes

出典と根拠

ORDレコード
ord-c8fca37c56124f79ab5b82cb5ac7327e
出典データセット
uspto-grants-2014_06
特許番号
US08754229B2

反応ノート

読み込み中…