Sodium Chloride → Methyl 4-amino-6-(2,5-difluoro-4-(trimethylsilyl)phenyl)-5-fluoro-3-methoxypicolinate

HRID 407233

反応式

HRID 407233 の反応式
[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[C:5]([F:17])=[CH:4][C:3]=1[Si:18]([CH3:21])([CH3:20])[CH3:19].[NH2:22][C:23]1[C:28]([F:29])=[C:27](Cl)[N:26]=[C:25]([C:31]([O:33][CH3:34])=[O:32])[C:24]=1[O:35][CH3:36].C([O-])([O-])=O.[Na+].[Na+].[Na+].[Cl-]>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.CC#N>[NH2:22][C:23]1[C:28]([F:29])=[C:27]([C:6]2[CH:7]=[C:2]([F:1])[C:3]([Si:18]([CH3:19])([CH3:20])[CH3:21])=[CH:4][C:5]=2[F:17])[N:26]=[C:25]([C:31]([O:33][CH3:34])=[O:32])[C:24]=1[O:35][CH3:36]

参加物

8

反応物 4

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 71150540(2,5-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)trimethylsilaneHCID 86675409Methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate

生成物 1

HCID 71150576Methyl 4-amino-6-(2,5-difluoro-4-(trimethylsilyl)phenyl)-5-fluoro-3-methoxypicolinate収率 60%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒

実験手順

(2,5-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)trimethylsilane (1.785 g, 4.69 mmol, 82% purity), methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate (1 g, 4.26 mmol), Na2CO3 (0.542 g, 5.11 mmol), and PdCl2(PPh3)2 (0.299 g, 0.426 mmol) were suspended in a 3:1 mixture of CH3CN (7.99 mL) and H2O (2.66 mL) in a microwave vial. The reaction mixture was irradiated at 90° C. for 20 min. The reaction was monitored by TLC and ultra performance liquid chromatography (HPLC). The mixture was poured into a half satd aq NaCl solution and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (SiO2, ISCO, 120 g column, hexanes/EtOAc gradient) to afford the title compound as a yellow solid (0.977 g, 60%): mp 137-139° C.; 1H NMR (400 MHz, CDCl3) δ 7.23 (dd, J=7.9, 5.1 Hz, 1H), 7.12 (dd, J=9.3, 4.0 Hz, 1H), 4.60 (s, 2H), 3.97 (s, 3H), 3.97 (s, 3H), 0.33 (d, J=0.8 Hz, 9H); 19F NMR (376 MHz, CDCl3) δ −107.12, −121.88, −137.27; ESIMS m/z 384 ([M]+).

後処理

  1. customThe reaction mixture was irradiated at 90° C. for 20 min
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (SiO2, ISCO, 120 g column, hexanes/EtOAc gradient)

出典と根拠

ORDレコード
ord-1b78a5f6f6764a198e4d748842ae487c
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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