Dichloromethane → (4-Methoxy-benzyl)-[4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]amine

HRID 1481541ノート

反応式

HRID 1481541 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[CH:5]=[C:4]([C:18]([F:21])([F:20])[F:19])[CH:3]=1.[F:22][C:23]([F:34])([F:33])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+].C(Cl)Cl>COCCOC.O>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][NH:8][C:6]2[CH:5]=[C:4]([C:18]([F:21])([F:20])[F:19])[CH:3]=[C:2]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[C:23]([F:34])([F:33])[F:22])[N:7]=2)=[CH:11][CH:12]=1

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 86657407(6-Chloro-4-trifluoromethyl-pyridin-2-yl)-(4-methoxy-benzyl)-amine

生成物 1

HCID 86657408(4-Methoxy-benzyl)-[4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]amine

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

A solution of (6-chloro-4-trifluoromethyl-pyridin-2-yl)-(4-methoxy-benzyl)-amine (7.26 g, 22.9 mmol, prepared as described in STEP A above) in DME (100 mL) and water (50 mL) was treated with 2-trifluoromethylphenylboronic acid (5.66 g, 29.8 mmol), and Cs2CO3 (11.2 g, 34.4 mmol). The resulting mixture was degassed via heating under a stream of Ar. Cl2Pd(dppf).DCM (1.13 g, 1.38 mmol) was added, and the mixture was heated to 80° C. for 4 h. The cooled mixture was diluted with water (100 mL) and extracted twice with EtOAc (150 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 115-g SEPRA Si 35 SPE column (Flow rate=30 mL/min; Eluent=EtOAc-hexanes, 1:99 for 10 min, then 1:99 to 1:4 over 40 min) to yield (4-methoxy-benzyl)-[4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amine as a yellow oil, which solidified upon standing. 1H-NMR (400 MHz, CDCl3) δ: 7.76 (d, J=7.8 Hz, 1H), 7.57-7.63 (m, 1H), 7.47-7.55 (m, 2H), 7.27 (d, J=8.6 Hz, 2H), 6.85-6.91 (m, 3H), 6.57 (s, 1H), 5.11 (t, J=5.2 Hz, 1H), 4.48 (d, J=5.6 Hz, 2H), 3.80 (s, 3H). Mass Spectrum (LCMS, APCI pos.): Calculated for C21H16N2OF6: 427.1 (M+H). Measured: 427.2.

後処理

  1. customThe resulting mixture was degassed
  2. temperaturevia heating under a stream of Ar
  3. extractionextracted twice with EtOAc (150 mL)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a 115-g SEPRA Si 35 SPE column (Flow rate=30 mL/min

出典と根拠

ORDレコード
ord-ea0be64668574385bad618be87910d21
出典データセット
uspto-grants-2016_08
特許番号
US09409915B2

反応ノート

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