Acetonitrile → Methyl 4-acetamido-3-chloro-6-(2,5-difluoro-4-(trimethylsilyl)phenyl)picolinate

HRID 516555

反応式

HRID 516555 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].[C:22]([NH:25][C:26]1[CH:31]=[C:30](Cl)[N:29]=[C:28]([C:33]([O:35][CH3:36])=[O:34])[C:27]=1[Cl:37])(=[O:24])[CH3:23].C(=O)([O-])[O-].[Na+].[Na+].C(#N)C>[Cl-].[Na+].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>[C:22]([NH:25][C:26]1[CH:31]=[C:30]([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:29]=[C:28]([C:33]([O:35][CH3:36])=[O:34])[C:27]=1[Cl:37])(=[O:24])[CH3:23]

参加物

8

反応物 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 22677481Methyl 4-acetamido-3,6-dichloropyridine-2-carboxylateHCID 71150540(2,5-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)trimethylsilane

生成物 1

HCID 90409198Methyl 4-acetamido-3-chloro-6-(2,5-difluoro-4-(trimethylsilyl)phenyl)picolinate収率 54.6%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
120 °C

実験手順

In a microwave vessel, a suspension of (2,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)trimethylsilane (see, e.g., WO 2013003740 A1) (1 g, 2.56 mmol), methyl 4-acetamido-3,6-dichloropicolinate (Head L) (0.562 g, 2.135 mmol), bis(triphenyl phosphine)palladium(II) chloride (0.150 g, 0.214 mmol) and sodium carbonate (0.272 g, 2.56 mmol) in a 3:1 mixture of acetonitrile (5.34 mL) and water (1.779 mL) was stirred under microwave irradiation (120° C., 20 min). The reaction mixture was poured into an half saturated brine solution and was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by preparative reverse phase HPLC (water/acetonitrile gradient) to afford the title compound as a white solid (0.481 g, 1.165 mmol, 54.6%): mp 135-137° C.; 1H NMR (400 MHz, CDCl3) δ 9.07 (d, J=0.8 Hz, 1H), 7.96 (s, 1H), 7.62 (dd, J=8.5, 5.7 Hz, 1H), 7.13 (dd, J=10.5, 4.1 Hz, 1H), 4.02 (s, 3H), 2.33 (s, 3H), 0.33 (d, J=0.8 Hz, 9H); 19F NMR (376 MHz, CDCl3) δ −106.66, −106.72, −123.42, −123.48; ESIMS m/z 411 ([M−H]−).

後処理

  1. extractionwas extracted with EtOAc (3×)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by preparative reverse phase HPLC (water/acetonitrile gradient)

出典と根拠

ORDレコード
ord-65fa0eb889eb4a4e8c6d9b968626abd7
出典データセット
uspto-grants-2015_08
特許番号
US09113629B2

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