Potassium Fluoride → Methyl 4-amino-6-(4-chlorophenyl)-5-fluoro-3-methoxypicolinate

HRID 407237

反応式

HRID 407237 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])[C:3]=1[O:14][CH3:15].[Cl:16][C:17]1[CH:22]=[CH:21][C:20](B2OCCCO2)=[CH:19][CH:18]=1.[F-].[K+].C1C=C(S([O-])(=O)=O)C=C(P(C2C=CC=C(S([O-])(=O)=O)C=2)C2C=CC=C(S([O-])(=O)=O)C=2)C=1.[Na+].[Na+].[Na+]>CC#N.O.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:20]2[CH:21]=[CH:22][C:17]([Cl:16])=[CH:18][CH:19]=2)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[O:14][CH3:15]

参加物

9

反応物 4

HCID 522689Potassium FluorideHCID 34689572-(4-Chlorophenyl)-1,3,2-dioxaborinaneHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)HCID 86675409Methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate

生成物 1

HCID 71150696Methyl 4-amino-6-(4-chlorophenyl)-5-fluoro-3-methoxypicolinate収率 72.2%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
150 °C

実験手順

To a solution of methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate (200 mg, 0.852 mmol) in CH3CN (1.246 mL) and H2O (1.246 mL) were added 2-(4-chlorophenyl)-1,3,2-dioxaborinane (251 mg, 1.279 mmol), KF (149 mg, 2.56 mmol), palladium(II) acetate (Pd(OAc)2; 19.14 mg, 0.085 mmol), and triphenylphosphine-3,3′,3″-trisulfonic acid trisodium salt (100 mg, 0.170 mmol). The reaction mixture was then heated in a bench top Biotage microwave at 150° C. for 5 min. The reaction mixture was diluted with CH2Cl2 and washed with H2O. The organic layer was separated, dried over MgSO4, filtered and concentrated. The crude residue was purified by normal phase chromatography (eluting with 10% EtOAc/40% CH2Cl2/50% hexanes) to afford the title compound as a tan solid (191 mg, 72.1%): mp 93-94° C.; 1H NMR (400 MHz, acetone-d6) δ 7.96 (dd, J=8.8, 1.4 Hz, 2H), 7.57-7.49 (m, 2H), 5.93 (s, 2H), 3.92 (s, 3H), 3.91 (s, 3H), ESIMS m/z 311 ([M+H]+), 309 ([M−H]−).

後処理

  1. washwashed with H2O
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by normal phase chromatography (eluting with 10% EtOAc/40% CH2Cl2/50% hexanes)

出典と根拠

ORDレコード
ord-9c18d074a7144da5a2d778269b02827d
出典データセット
uspto-grants-2014_06
特許番号
US08754229B2

関連ノート

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