Citric Acid → N-Methyl-N-(6-methyl-4-o-tolyl-pyridin-3-yl)-3,5-bis-trifluoromethyl-benzamide

HRID 878131ノート

反応式

HRID 878131 の反応式
Cl[C:2]1[N:7]=[CH:6][C:5]([N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=2)=[C:4]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[CH3:32])[CH:3]=1.[Cl-].C[Zn+].[CH3:36]N1CCN(C)C1=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CC(C1C=CC=C(C(C)C)C=1N1[CH-]N(C2C(C(C)C)=CC=CC=2C(C)C)CC1)C.C1C=NC=C(Cl)C=1.Cl[Pd]Cl.CCOC(C)=O>[CH3:25][N:8]([C:5]1[CH:6]=[N:7][C:2]([CH3:36])=[CH:3][C:4]=1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH3:32])[C:9](=[O:24])[C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=1

参加物

8

反応物 4

HCID 311Citric AcidHCID 66611,3-Dimethyl-2-imidazolidinoneHCID 60197100N-(6-Chloro-4-o-tolyl-pyridin-3-yl)-N-methyl-3,5-bis-trifluoromethyl-benzamideHCID 178477797HCID 178477797、化合物

生成物 1

HCID 86670748N-Methyl-N-(6-methyl-4-o-tolyl-pyridin-3-yl)-3,5-bis-trifluoromethyl-benzamide

試薬・触媒・溶媒 3

HCID 588388791,3-Bis[2,6-di(propan-2-yl)phenyl]imidazolidin-2-ide;3-chloropyridine;dichloropalladium触媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

To a solution of N-(6-chloro-4-o-tolyl-pyridin-3-yl)-N-methyl-3,5-bis-trifluoromethyl-benzamide (0.15 g, 0.317 mmol, example 12) in THF (2 mL) were added methylzinc chloride (0.238 mL, 0.476 mmol, 2M solution in THF), 1,3-dimethyl-2-imidazolidinone (0.4 mL, CAS RN 80-73-9) and (1,3-bis(2,6-diisopropylphenyl)imidazolidene) (3-chloropyridyl)palladium(II) dichloride (4.31 mg, 0.00635 mmol, Sigma-Aldrich) and the reaction was stirred at 50° C. (oil bath temperature) for 1 h. The reaction mixture was poured on 10% aqueous citric acid solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc and the organic layers were washed with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 10 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). Colorless oil (0.122 g; 85%). MS (ESI): m/z=453.14 [M+H]+.

後処理

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted twice with EtOAc
  3. washthe organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. additiontreated with silica gel
  7. customevaporated
  8. customThe compound was purified by silica gel chromatography on a 10 g column
  9. washeluting with a gradient of n-heptane:EtOAc (100:0 to 50:50)

出典と根拠

ORDレコード
ord-64dffa1722b84c568825df8db32a1f95
出典データセット
uspto-grants-2015_03
特許番号
US08987307B2

反応ノート

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